Trial Outcomes & Findings for A Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder (NCT NCT04512066)
NCT ID: NCT04512066
Last Updated: 2023-10-10
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
287 participants
Primary outcome timeframe
Week 4 (Day 28)
Results posted on
2023-10-10
Participant Flow
287 participants initially randomized in the double-blind treatment period. 11 excluded from final analysis due to having not received assigned study medication or because of re-enrollment. Participants were not required to participate in all study parts and those that did not continue to the double-blind treatment period either discontinued the study during the double-blind treatment period or exited the study after completing the period. 197 continued to the double-blind extension period.
Participant milestones
| Measure |
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.
|
RO6889450 45 mg
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Double-blind Treatment Period
STARTED
|
73
|
71
|
69
|
74
|
0
|
0
|
|
Double-blind Treatment Period
COMPLETED
|
56
|
55
|
53
|
60
|
0
|
0
|
|
Double-blind Treatment Period
NOT COMPLETED
|
17
|
16
|
16
|
14
|
0
|
0
|
|
Extension Period
STARTED
|
0
|
44
|
46
|
56
|
25
|
26
|
|
Extension Period
COMPLETED
|
0
|
30
|
26
|
38
|
9
|
12
|
|
Extension Period
NOT COMPLETED
|
0
|
14
|
20
|
18
|
16
|
14
|
Reasons for withdrawal
| Measure |
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.
|
RO6889450 45 mg
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Double-blind Treatment Period
Adverse Event
|
6
|
4
|
5
|
1
|
0
|
0
|
|
Double-blind Treatment Period
Lack of Efficacy
|
3
|
3
|
5
|
1
|
0
|
0
|
|
Double-blind Treatment Period
Physician Decision
|
1
|
0
|
1
|
0
|
0
|
0
|
|
Double-blind Treatment Period
Withdrawal by Subject
|
7
|
9
|
5
|
12
|
0
|
0
|
|
Extension Period
Adverse Event
|
0
|
1
|
4
|
3
|
1
|
3
|
|
Extension Period
Death
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Extension Period
Lack of Efficacy
|
0
|
4
|
4
|
1
|
3
|
3
|
|
Extension Period
Lost to Follow-up
|
0
|
1
|
5
|
2
|
3
|
2
|
|
Extension Period
Non-compliance with study drug
|
0
|
1
|
0
|
0
|
0
|
1
|
|
Extension Period
Other
|
0
|
2
|
0
|
0
|
0
|
0
|
|
Extension Period
Physician Decision
|
0
|
2
|
0
|
1
|
1
|
0
|
|
Extension Period
Withdrawal by Subject
|
0
|
3
|
7
|
11
|
8
|
4
|
Baseline Characteristics
A Trial of the Efficacy and the Safety of RO6889450 (Ralmitaront) vs Placebo in Patients With an Acute Exacerbation of Schizophrenia or Schizoaffective Disorder
Baseline characteristics by cohort
| Measure |
Placebo
n=72 Participants
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.
|
RO6889450 45 mg
n=65 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=68 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=71 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Total
n=276 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
33.2 Years
STANDARD_DEVIATION 7.1 • n=99 Participants
|
34.0 Years
STANDARD_DEVIATION 7.0 • n=107 Participants
|
32.3 Years
STANDARD_DEVIATION 6.5 • n=206 Participants
|
32.9 Years
STANDARD_DEVIATION 7.1 • n=7 Participants
|
33.1 Years
STANDARD_DEVIATION 6.9 • n=31 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
15 Participants
n=206 Participants
|
18 Participants
n=7 Participants
|
71 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
53 Participants
n=99 Participants
|
46 Participants
n=107 Participants
|
53 Participants
n=206 Participants
|
53 Participants
n=7 Participants
|
205 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
10 Participants
n=7 Participants
|
37 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
64 Participants
n=99 Participants
|
54 Participants
n=107 Participants
|
60 Participants
n=206 Participants
|
61 Participants
n=7 Participants
|
239 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
33 Participants
n=99 Participants
|
27 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
31 Participants
n=7 Participants
|
123 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
37 Participants
n=99 Participants
|
35 Participants
n=107 Participants
|
32 Participants
n=206 Participants
|
39 Participants
n=7 Participants
|
143 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
2 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Week 4 (Day 28)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=72 Participants
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.
|
RO6889450 45 mg
n=65 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=68 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=71 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
Day 28
|
88.69 Units on a scale
Standard Deviation 20.18
|
88.94 Units on a scale
Standard Deviation 17.03
|
85.18 Units on a scale
Standard Deviation 17.67
|
78.04 Units on a scale
Standard Deviation 15.78
|
—
|
|
Mean Change From Baseline in the Positive and Negative Syndrome Scale (PANSS) Total Score at Week 4
Baseline
|
99.38 Units on a scale
Standard Deviation 11.36
|
98.54 Units on a scale
Standard Deviation 9.51
|
100.53 Units on a scale
Standard Deviation 12.25
|
100.03 Units on a scale
Standard Deviation 10.56
|
—
|
SECONDARY outcome
Timeframe: Week 4 (Day 28)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=72 Participants
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.
|
RO6889450 45 mg
n=65 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=68 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=71 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
Change From Baseline in PANSS Factor Scores at Week 4
Anxiety/Depression - Baseline
|
11.58 Units on a scale
Standard Deviation 3.39
|
12.91 Units on a scale
Standard Deviation 2.92
|
11.54 Units on a scale
Standard Deviation 3.40
|
12.58 Units on a scale
Standard Deviation 3.67
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Anxiety/Depression - Day 28
|
9.56 Units on a scale
Standard Deviation 4.03
|
9.88 Units on a scale
Standard Deviation 4.15
|
9.06 Units on a scale
Standard Deviation 4.08
|
8.50 Units on a scale
Standard Deviation 4.09
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Disorganized thought/Cognition - Baseline
|
21.86 Units on a scale
Standard Deviation 4.43
|
21.43 Units on a scale
Standard Deviation 4.66
|
22.50 Units on a scale
Standard Deviation 4.82
|
21.45 Units on a scale
Standard Deviation 4.87
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Disorganized thought/Cognition - Day 28
|
19.69 Units on a scale
Standard Deviation 6.25
|
20.63 Units on a scale
Standard Deviation 4.94
|
19.41 Units on a scale
Standard Deviation 6.44
|
17.07 Units on a scale
Standard Deviation 4.66
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Positive symptom factor score - Day 28
|
27.72 Units on a scale
Standard Deviation 7.03
|
28.06 Units on a scale
Standard Deviation 6.14
|
26.63 Units on a scale
Standard Deviation 7.16
|
24.21 Units on a scale
Standard Deviation 5.38
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Avolition - Baseline
|
15.99 Units on a scale
Standard Deviation 3.16
|
15.86 Units on a scale
Standard Deviation 2.83
|
16.38 Units on a scale
Standard Deviation 3.25
|
16.20 Units on a scale
Standard Deviation 2.73
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Avolition - Day 28
|
14.04 Units on a scale
Standard Deviation 3.70
|
13.67 Units on a scale
Standard Deviation 4.42
|
13.73 Units on a scale
Standard Deviation 3.69
|
12.93 Units on a scale
Standard Deviation 3.44
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Expressive deficit - Baseline
|
10.89 Units on a scale
Standard Deviation 3.97
|
10.31 Units on a scale
Standard Deviation 3.96
|
10.90 Units on a scale
Standard Deviation 3.79
|
10.23 Units on a scale
Standard Deviation 3.43
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Expressive deficit - Day 28
|
10.81 Units on a scale
Standard Deviation 4.01
|
10.69 Units on a scale
Standard Deviation 4.39
|
10.16 Units on a scale
Standard Deviation 4.18
|
10.71 Units on a scale
Standard Deviation 3.67
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Totals general - Baseline
|
48.42 Units on a scale
Standard Deviation 6.24
|
48.69 Units on a scale
Standard Deviation 5.49
|
48.68 Units on a scale
Standard Deviation 6.57
|
48.89 Units on a scale
Standard Deviation 6.29
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Totals general - Day 28
|
42.43 Units on a scale
Standard Deviation 10.68
|
43.71 Units on a scale
Standard Deviation 9.06
|
40.43 Units on a scale
Standard Deviation 8.94
|
37.07 Units on a scale
Standard Deviation 8.12
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Negative symptom factor score - Baseline
|
23.58 Units on a scale
Standard Deviation 5.44
|
23.02 Units on a scale
Standard Deviation 5.19
|
23.81 Units on a scale
Standard Deviation 5.36
|
23.34 Units on a scale
Standard Deviation 4.55
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Negative symptom factor score - Day 28
|
21.63 Units on a scale
Standard Deviation 6.04
|
21.27 Units on a scale
Standard Deviation 6.63
|
20.80 Units on a scale
Standard Deviation 5.70
|
20.39 Units on a scale
Standard Deviation 5.55
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Totals negative - Baseline
|
24.10 Units on a scale
Standard Deviation 5.29
|
23.65 Units on a scale
Standard Deviation 4.50
|
24.59 Units on a scale
Standard Deviation 4.87
|
23.65 Units on a scale
Standard Deviation 3.78
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Totals negative - Day 28
|
22.65 Units on a scale
Standard Deviation 5.81
|
21.82 Units on a scale
Standard Deviation 5.85
|
22.53 Units on a scale
Standard Deviation 5.41
|
21.45 Units on a scale
Standard Deviation 5.13
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Positive symptom factor score - Baseline
|
31.40 Units on a scale
Standard Deviation 3.59
|
30.66 Units on a scale
Standard Deviation 3.84
|
32.03 Units on a scale
Standard Deviation 4.89
|
31.15 Units on a scale
Standard Deviation 3.73
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Totals positive - Baseline
|
26.86 Units on a scale
Standard Deviation 3.60
|
26.20 Units on a scale
Standard Deviation 4.19
|
27.26 Units on a scale
Standard Deviation 5.13
|
27.49 Units on a scale
Standard Deviation 3.95
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Totals positive - Day 28
|
23.61 Units on a scale
Standard Deviation 6.64
|
23.41 Units on a scale
Standard Deviation 6.14
|
22.22 Units on a scale
Standard Deviation 6.50
|
19.52 Units on a scale
Standard Deviation 5.11
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Uncontrolled hostility/excitement - Baseline
|
10.94 Units on a scale
Standard Deviation 3.94
|
10.52 Units on a scale
Standard Deviation 4.07
|
10.65 Units on a scale
Standard Deviation 4.12
|
11.51 Units on a scale
Standard Deviation 3.90
|
—
|
|
Change From Baseline in PANSS Factor Scores at Week 4
Uncontrolled hostility/excitement - Day 28
|
10.09 Units on a scale
Standard Deviation 4.83
|
9.10 Units on a scale
Standard Deviation 4.33
|
9.27 Units on a scale
Standard Deviation 4.22
|
7.86 Units on a scale
Standard Deviation 4.06
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=72 Participants
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.
|
RO6889450 45 mg
n=65 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=68 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=71 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score
20% improvement - Week 1
|
18.1 Proportion expressed as percentage
|
26.2 Proportion expressed as percentage
|
27.9 Proportion expressed as percentage
|
25.4 Proportion expressed as percentage
|
—
|
|
Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score
20% improvement - Week 2
|
26.4 Proportion expressed as percentage
|
24.6 Proportion expressed as percentage
|
36.8 Proportion expressed as percentage
|
43.7 Proportion expressed as percentage
|
—
|
|
Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score
20% improvement - Week 3
|
31.9 Proportion expressed as percentage
|
32.3 Proportion expressed as percentage
|
38.2 Proportion expressed as percentage
|
59.2 Proportion expressed as percentage
|
—
|
|
Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score
20% improvement - Week 4
|
30.6 Proportion expressed as percentage
|
32.3 Proportion expressed as percentage
|
36.8 Proportion expressed as percentage
|
59.2 Proportion expressed as percentage
|
—
|
|
Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score
50% improvement - Week 1
|
0 Proportion expressed as percentage
|
1.5 Proportion expressed as percentage
|
1.5 Proportion expressed as percentage
|
2.8 Proportion expressed as percentage
|
—
|
|
Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score
50% improvement - Week 2
|
2.8 Proportion expressed as percentage
|
3.1 Proportion expressed as percentage
|
4.4 Proportion expressed as percentage
|
4.2 Proportion expressed as percentage
|
—
|
|
Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score
50% improvement - Week 3
|
2.8 Proportion expressed as percentage
|
7.7 Proportion expressed as percentage
|
2.9 Proportion expressed as percentage
|
14.1 Proportion expressed as percentage
|
—
|
|
Proportion of Participants With at Least 20% or 50% Improvement From Baseline in the PANSS Total Score
50% improvement - Week 4
|
8.3 Proportion expressed as percentage
|
7.7 Proportion expressed as percentage
|
8.8 Proportion expressed as percentage
|
14.1 Proportion expressed as percentage
|
—
|
SECONDARY outcome
Timeframe: Week 4 (Day 28)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=72 Participants
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.
|
RO6889450 45 mg
n=65 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=68 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=71 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores
Baseline
|
5.13 Units on a scale
Standard Deviation 0.50
|
5.09 Units on a scale
Standard Deviation 0.52
|
5.25 Units on a scale
Standard Deviation 0.63
|
5.27 Units on a scale
Standard Deviation 0.61
|
—
|
|
Change From Baseline in Clinical Global Impression Severity (CGI-S) Scores
Day 28
|
4.42 Units on a scale
Standard Deviation 1.07
|
4.35 Units on a scale
Standard Deviation 0.99
|
4.29 Units on a scale
Standard Deviation 0.85
|
3.88 Units on a scale
Standard Deviation 0.94
|
—
|
SECONDARY outcome
Timeframe: Week 4 (Day 28)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=69 Participants
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.
|
RO6889450 45 mg
n=60 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=66 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=68 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
Clinical Global Impression - Improvement (CGI-I) Scores
Day 7
|
3.87 Units on a scale
Standard Deviation 0.86
|
3.60 Units on a scale
Standard Deviation 0.76
|
3.56 Units on a scale
Standard Deviation 0.88
|
3.40 Units on a scale
Standard Deviation 0.87
|
—
|
|
Clinical Global Impression - Improvement (CGI-I) Scores
Day 14
|
3.63 Units on a scale
Standard Deviation 0.94
|
3.39 Units on a scale
Standard Deviation 0.95
|
3.33 Units on a scale
Standard Deviation 0.90
|
2.99 Units on a scale
Standard Deviation 1.01
|
—
|
|
Clinical Global Impression - Improvement (CGI-I) Scores
Day 21
|
3.47 Units on a scale
Standard Deviation 1.19
|
3.28 Units on a scale
Standard Deviation 1.06
|
3.13 Units on a scale
Standard Deviation 1.06
|
2.79 Units on a scale
Standard Deviation 1.01
|
—
|
|
Clinical Global Impression - Improvement (CGI-I) Scores
Day 28
|
3.27 Units on a scale
Standard Deviation 1.29
|
3.27 Units on a scale
Standard Deviation 1.17
|
2.96 Units on a scale
Standard Deviation 0.93
|
2.43 Units on a scale
Standard Deviation 0.89
|
—
|
SECONDARY outcome
Timeframe: Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=25 Participants
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.
|
RO6889450 45 mg
n=25 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=41 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=45 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=53 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
PANSS Total Score at Week 12
Baseline
|
103.44 Units on a scale
Standard Deviation 12.58
|
99.12 Units on a scale
Standard Deviation 10.16
|
98.66 Units on a scale
Standard Deviation 9.64
|
99.00 Units on a scale
Standard Deviation 11.37
|
100.30 Units on a scale
Standard Deviation 11.49
|
|
PANSS Total Score at Week 12
Week 12
|
75.10 Units on a scale
Standard Deviation 17.53
|
76.73 Units on a scale
Standard Deviation 21.09
|
76.25 Units on a scale
Standard Deviation 17.89
|
79.30 Units on a scale
Standard Deviation 13.68
|
67.74 Units on a scale
Standard Deviation 11.50
|
SECONDARY outcome
Timeframe: Weeks 4, 8, and 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=25 Participants
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.
|
RO6889450 45 mg
n=25 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=41 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=45 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=53 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12
Week 4
|
40.0 Proportion expressed as a percentage
|
36.0 Proportion expressed as a percentage
|
46.3 Proportion expressed as a percentage
|
53.3 Proportion expressed as a percentage
|
75.5 Proportion expressed as a percentage
|
|
Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12
Week 8
|
36.0 Proportion expressed as a percentage
|
28.0 Proportion expressed as a percentage
|
43.9 Proportion expressed as a percentage
|
37.8 Proportion expressed as a percentage
|
69.8 Proportion expressed as a percentage
|
|
Proportion of Participants With at Least 20% or 50% Improvement in the PANSS Total Score up to Week 12
Week 12
|
28.0 Proportion expressed as a percentage
|
28.0 Proportion expressed as a percentage
|
48.8 Proportion expressed as a percentage
|
28.9 Proportion expressed as a percentage
|
50.9 Proportion expressed as a percentage
|
SECONDARY outcome
Timeframe: Up to Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=25 Participants
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.
|
RO6889450 45 mg
n=25 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=41 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=45 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=53 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
CGI-S up to Week 12
Week 12
|
3.33 Units on a scale
Standard Deviation 1.00
|
3.73 Units on a scale
Standard Deviation 1.27
|
3.56 Units on a scale
Standard Deviation 1.01
|
3.90 Units on a scale
Standard Deviation 0.85
|
3.06 Units on a scale
Standard Deviation 0.81
|
|
CGI-S up to Week 12
Baseline
|
5.28 Units on a scale
Standard Deviation 0.54
|
5.16 Units on a scale
Standard Deviation 0.47
|
5.05 Units on a scale
Standard Deviation 0.50
|
5.16 Units on a scale
Standard Deviation 0.60
|
5.26 Units on a scale
Standard Deviation 0.62
|
SECONDARY outcome
Timeframe: Up to Week 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=25 Participants
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.
|
RO6889450 45 mg
n=25 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=41 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=45 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=53 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
CGI-I up to Week 12
Day 7
|
3.54 Units on a scale
Standard Deviation 0.66
|
3.76 Units on a scale
Standard Deviation 0.78
|
3.54 Units on a scale
Standard Deviation 0.78
|
3.56 Units on a scale
Standard Deviation 0.84
|
3.38 Units on a scale
Standard Deviation 0.84
|
|
CGI-I up to Week 12
Week 12
|
2.33 Units on a scale
Standard Deviation 1.00
|
2.73 Units on a scale
Standard Deviation 1.56
|
2.30 Units on a scale
Standard Deviation 0.91
|
2.65 Units on a scale
Standard Deviation 0.93
|
2.00 Units on a scale
Standard Deviation 0.82
|
SECONDARY outcome
Timeframe: after 4-week treatmentPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=64 Participants
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.
|
RO6889450 45 mg
n=54 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=61 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=69 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
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
|
88.9 Percentage of participants
Interval 79.3 to 95.1
|
83.1 Percentage of participants
Interval 71.7 to 91.2
|
89.7 Percentage of participants
Interval 79.9 to 95.8
|
97.2 Percentage of participants
Interval 90.2 to 99.7
|
—
|
SECONDARY outcome
Timeframe: Day 7 - Day 336Population: 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.
Outcome measures
| Measure |
Placebo
n=25 Participants
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.
|
RO6889450 45 mg
n=25 Participants
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg
n=71 Participants
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
n=69 Participants
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|
|
Plasma Concentration of RO6889450
Day 7
|
—
|
—
|
99.50 ng/mL
Geometric Coefficient of Variation 69.2
|
423.83 ng/mL
Geometric Coefficient of Variation 43.2
|
—
|
|
Plasma Concentration of RO6889450
Day 14
|
—
|
—
|
91.53 ng/mL
Geometric Coefficient of Variation 111.4
|
463.21 ng/mL
Geometric Coefficient of Variation 73.6
|
—
|
|
Plasma Concentration of RO6889450
Day 28
|
49.67 ng/mL
Geometric Coefficient of Variation 155.4
|
212.27 ng/mL
Geometric Coefficient of Variation 25.0
|
94.57 ng/mL
Geometric Coefficient of Variation 108.1
|
419.41 ng/mL
Geometric Coefficient of Variation 93.0
|
—
|
|
Plasma Concentration of RO6889450
Day 42
|
59.99 ng/mL
Geometric Coefficient of Variation 248.3
|
274.58 ng/mL
Geometric Coefficient of Variation 208.8
|
108.57 ng/mL
Geometric Coefficient of Variation 76.4
|
390.65 ng/mL
Geometric Coefficient of Variation 138.4
|
—
|
|
Plasma Concentration of RO6889450
Day 56
|
70.99 ng/mL
Geometric Coefficient of Variation 320.4
|
217.65 ng/mL
Geometric Coefficient of Variation 491.6
|
108.59 ng/mL
Geometric Coefficient of Variation 55.5
|
237.42 ng/mL
Geometric Coefficient of Variation 541.2
|
—
|
|
Plasma Concentration of RO6889450
Day 84
|
77.11 ng/mL
Geometric Coefficient of Variation 85.5
|
165.99 ng/mL
Geometric Coefficient of Variation 963.0
|
92.24 ng/mL
Geometric Coefficient of Variation 128.5
|
265.09 ng/mL
Geometric Coefficient of Variation 353.6
|
—
|
|
Plasma Concentration of RO6889450
Day 168
|
—
|
—
|
95.39 ng/mL
Geometric Coefficient of Variation 46.0
|
733.98 ng/mL
Geometric Coefficient of Variation 65.5
|
—
|
|
Plasma Concentration of RO6889450
Day 336
|
—
|
—
|
4.13 ng/mL
Geometric Coefficient of Variation NA
The value was not estimable for data from a single participant.
|
139.71 ng/mL
Geometric Coefficient of Variation 120.6
|
—
|
Adverse Events
Placebo
Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths
RO6889450 45 mg (Double-blind Treatment Period)
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
RO6889450 150 mg (Double-blind Treatment Period)
Serious events: 1 serious events
Other events: 23 other events
Deaths: 0 deaths
Risperidone 4 mg (Double-blind Treatment Period)
Serious events: 0 serious events
Other events: 36 other events
Deaths: 0 deaths
Placebo - RO6889450 45 mg
Serious events: 3 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo - RO6889450 150 mg
Serious events: 3 serious events
Other events: 6 other events
Deaths: 1 deaths
RO6889450 45 mg (Extension Period)
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
RO6889450 150 mg (Extension Period)
Serious events: 6 serious events
Other events: 12 other events
Deaths: 0 deaths
Risperidone 4 mg (Extension Period)
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=72 participants at risk
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.
|
RO6889450 45 mg (Double-blind Treatment Period)
n=65 participants at risk
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg (Double-blind Treatment Period)
n=68 participants at risk
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg (Double-blind Treatment Period)
n=71 participants at risk
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Placebo - RO6889450 45 mg
n=25 participants at risk
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.
|
Placebo - RO6889450 150 mg
n=25 participants at risk
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.
|
RO6889450 45 mg (Extension Period)
n=41 participants at risk
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg (Extension Period)
n=45 participants at risk
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg (Extension Period)
n=53 participants at risk
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|---|---|---|---|
|
Psychiatric disorders
Schizophrenia
|
1.4%
1/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
3.1%
2/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
12.0%
3/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
8.0%
2/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.4%
1/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
11.1%
5/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Psychiatric disorders
Psychotic disorder
|
0.00%
0/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
1.5%
1/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.2%
1/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
1.9%
1/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Injury, poisoning and procedural complications
Gun shot wound
|
0.00%
0/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
4.0%
1/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
Other adverse events
| Measure |
Placebo
n=72 participants at risk
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.
|
RO6889450 45 mg (Double-blind Treatment Period)
n=65 participants at risk
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg (Double-blind Treatment Period)
n=68 participants at risk
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg (Double-blind Treatment Period)
n=71 participants at risk
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
Placebo - RO6889450 45 mg
n=25 participants at risk
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.
|
Placebo - RO6889450 150 mg
n=25 participants at risk
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.
|
RO6889450 45 mg (Extension Period)
n=41 participants at risk
Participants received 45 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
RO6889450 150 mg (Extension Period)
n=45 participants at risk
Participants received 150 mg of RO6889450 QD for 4, 12, or 48 weeks.
|
Risperidone 4 mg (Extension Period)
n=53 participants at risk
Participants received 4 mg of risperidone QD for 4, 12, or 48 weeks.
|
|---|---|---|---|---|---|---|---|---|---|
|
Psychiatric disorders
Anxiety
|
8.3%
6/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
4.6%
3/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.9%
2/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
7.0%
5/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.2%
1/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Psychiatric disorders
Insomnia
|
1.4%
1/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
4.6%
3/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
7.4%
5/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
7.0%
5/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.4%
1/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.2%
1/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Psychiatric disorders
Agitation
|
2.8%
2/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
11.8%
8/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
4.0%
1/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Nervous system disorders
Headache
|
5.6%
4/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
6.2%
4/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
7.4%
5/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
8.5%
6/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
4.9%
2/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.2%
1/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
1.9%
1/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Gastrointestinal disorders
Nausea
|
5.6%
4/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.9%
2/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
8.5%
6/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
4.0%
1/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.4%
1/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
4.4%
2/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Gastrointestinal disorders
Vomiting
|
2.8%
2/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
1.5%
1/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
7.0%
5/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.4%
1/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.2%
1/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Investigations
Weight increased
|
1.4%
1/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
3.1%
2/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
11.3%
8/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
4.0%
1/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
4.0%
1/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
2.2%
1/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
7.5%
4/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
|
Psychiatric disorders
Schizophrenia
|
4.2%
3/72 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
3.1%
2/65 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/68 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
1.4%
1/71 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
16.0%
4/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
12.0%
3/25 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
4.9%
2/41 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
11.1%
5/45 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
0.00%
0/53 • 4 weeks for double-blind treatment period Up to 48 weeks for extension period
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER