Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Risperidone ISM® in Patients With Acute Schizophrenia: Open Label Extension (NCT NCT03870880)
NCT ID: NCT03870880
Last Updated: 2022-03-25
Results Overview
The Positive and Negative Syndrome Scale (PANSS) is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia.The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicates improvements in symptoms whereas higher scores mean a worse outcome. Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
215 participants
Primary outcome timeframe
Baseline and Day 365 (or the last post-baseline assessment)
Results posted on
2022-03-25
Participant Flow
Patients enter the study as rollover patients from the previous double-blind (DB) study (NCT03160521), along with newly enrolled de novo patients. Rollover patients received Risperidone ISM in the OLE study at the same dose as during the DB study (75 mg or 100 mg). Patients who received placebo in the DB were assigned to receive either Risperidone ISM 75 or 100 mg during the OLE. De novo patients received either Risperidone ISM 75 or 100 mg depending on the previous oral risperidone treatment.
Participant milestones
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM in the OLE study. Their previous oral risperidone was more than 4 mg/day to a maximum of 6 mg/day.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
27
|
58
|
31
|
28
|
61
|
10
|
|
Overall Study
COMPLETED
|
21
|
43
|
26
|
20
|
44
|
7
|
|
Overall Study
NOT COMPLETED
|
6
|
15
|
5
|
8
|
17
|
3
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Evaluate the Efficacy and Safety of Risperidone ISM® in Patients With Acute Schizophrenia: Open Label Extension
Baseline characteristics by cohort
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=27 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=58 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
n=31 Participants
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
n=28 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
n=61 Participants
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
n=10 Participants
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM in the OLE study. Their previous oral risperidone was more than 4 mg/day to a maximum of 6 mg/day.
|
Total
n=215 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Time since Acute Exacerbation or relapse (weeks)
|
0.4 Weeks
STANDARD_DEVIATION 0.18 • n=5 Participants
|
0.3 Weeks
STANDARD_DEVIATION 0.21 • n=7 Participants
|
0 Weeks
STANDARD_DEVIATION 0 • n=5 Participants
|
0.4 Weeks
STANDARD_DEVIATION 0.20 • n=4 Participants
|
0.4 Weeks
STANDARD_DEVIATION 0.24 • n=21 Participants
|
0 Weeks
STANDARD_DEVIATION 0 • n=10 Participants
|
0.4 Weeks
STANDARD_DEVIATION 0.21 • n=115 Participants
|
|
Age, Continuous
|
38.7 years
STANDARD_DEVIATION 9.29 • n=5 Participants
|
40.9 years
STANDARD_DEVIATION 11.98 • n=7 Participants
|
37.0 years
STANDARD_DEVIATION 10.91 • n=5 Participants
|
38.4 years
STANDARD_DEVIATION 10.42 • n=4 Participants
|
40.3 years
STANDARD_DEVIATION 11.04 • n=21 Participants
|
35.5 years
STANDARD_DEVIATION 6.40 • n=10 Participants
|
39.3 years
STANDARD_DEVIATION 10.84 • n=115 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
17 Participants
n=4 Participants
|
23 Participants
n=21 Participants
|
6 Participants
n=10 Participants
|
84 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
38 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
131 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
8 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
26 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
26 Participants
n=4 Participants
|
61 Participants
n=21 Participants
|
10 Participants
n=10 Participants
|
207 Participants
n=115 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
1 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
14 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
32 Participants
n=115 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
47 Participants
n=21 Participants
|
10 Participants
n=10 Participants
|
182 Participants
n=115 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
11 participants
n=7 Participants
|
0 participants
n=5 Participants
|
6 participants
n=4 Participants
|
16 participants
n=21 Participants
|
0 participants
n=10 Participants
|
40 participants
n=115 Participants
|
|
Region of Enrollment
Ukraine
|
20 participants
n=5 Participants
|
47 participants
n=7 Participants
|
31 participants
n=5 Participants
|
22 participants
n=4 Participants
|
45 participants
n=21 Participants
|
10 participants
n=10 Participants
|
175 participants
n=115 Participants
|
|
Body Mass Index (BMI)
|
27.53 Kg/m^2
STANDARD_DEVIATION 4.488 • n=5 Participants
|
26.52 Kg/m^2
STANDARD_DEVIATION 4.741 • n=7 Participants
|
25.28 Kg/m^2
STANDARD_DEVIATION 3.695 • n=5 Participants
|
27.65 Kg/m^2
STANDARD_DEVIATION 4.954 • n=4 Participants
|
27.53 Kg/m^2
STANDARD_DEVIATION 5.055 • n=21 Participants
|
26.06 Kg/m^2
STANDARD_DEVIATION 3.937 • n=10 Participants
|
26.88 Kg/m^2
STANDARD_DEVIATION 4.685 • n=115 Participants
|
|
Years since Schizophrenia Diagnosis
|
11.8 years
STANDARD_DEVIATION 6.81 • n=5 Participants
|
12.1 years
STANDARD_DEVIATION 9.17 • n=7 Participants
|
9.6 years
STANDARD_DEVIATION 8.12 • n=5 Participants
|
9.3 years
STANDARD_DEVIATION 7.45 • n=4 Participants
|
11.5 years
STANDARD_DEVIATION 7.98 • n=21 Participants
|
6.4 years
STANDARD_DEVIATION 5.34 • n=10 Participants
|
10.9 years
STANDARD_DEVIATION 8.09 • n=115 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
The Positive and Negative Syndrome Scale (PANSS) is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia.The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score is the sum of all 30 PANSS items and ranges from 30 to 210, with 30 indicating absence of symptoms of schizophrenia and 210 indicating extreme ratings of all 30 symptoms. Negative change from baseline scores indicates improvements in symptoms whereas higher scores mean a worse outcome. Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=27 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=58 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
n=31 Participants
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
n=28 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
n=61 Participants
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
n=10 Participants
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
PANSS Total Score Mean Change From Baseline to Endpoint
|
-22.9 units on a scale
Standard Deviation 14.15
|
-11.0 units on a scale
Standard Deviation 14.52
|
-0.8 units on a scale
Standard Deviation 9.39
|
-18.9 units on a scale
Standard Deviation 14.61
|
-8.7 units on a scale
Standard Deviation 13.29
|
-4.8 units on a scale
Standard Deviation 4.80
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. In positive subscale, the 7 positive symptom constructs were: delusions, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, and hostility. PANSS Positive Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=27 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=58 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
n=31 Participants
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
n=28 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
n=61 Participants
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
n=10 Participants
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
PANSS Positive Subscale Mean Change From Baseline to Endpoint
|
-6.0 units on a scale
Standard Deviation 4.84
|
-3.3 units on a scale
Standard Deviation 5.47
|
-0.6 units on a scale
Standard Deviation 3.32
|
-6.5 units on a scale
Standard Deviation 5.32
|
-2.6 units on a scale
Standard Deviation 4.75
|
-1.6 units on a scale
Standard Deviation 2.67
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
The PANSS consisted of three subscales: a total of 30 symptom constructs. For each symptom construct, severity was rated on a 7-point scale, with a score of 1 indicated- absence of symptoms and a score of 7 indicated- extremely severe symptoms. The PANSS negative subscale score was the sum of the rating scores for the 7 negative scale items from the PANSS panel. The 7 negative symptom constructs were: blunted affect, emotional withdrawal, poor rapport, passive apathetic withdrawal, difficulty in abstract thinking, lack of spontaneity and flow of conversation and stereotyped thinking. PANSS Negative Subscale Score ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=27 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=58 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
n=31 Participants
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
n=28 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
n=61 Participants
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
n=10 Participants
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
PANSS Negative Subscale Mean Change From Baseline to Endpoint
|
-4.6 units on a scale
Standard Deviation 5.24
|
-2.2 units on a scale
Standard Deviation 3.61
|
-0.3 units on a scale
Standard Deviation 3.21
|
-2.9 units on a scale
Standard Deviation 3.75
|
-2.1 units on a scale
Standard Deviation 3.66
|
-0.7 units on a scale
Standard Deviation 4.22
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
The PANSS consisted of three subscales that contained a total of 30 symptom constructs. For each symptom construct, severity is rated on a 7-point scale, with a score of 1 indicated the absence of symptoms and a score of 7 indicated extremely severe symptoms. The general psychopathology scale consists of 16 items which measure somatic concern, anxiety, guilt feelings, tension, mannerisms and posturing, depression, motor retardation, uncooperativeness, unusual thought content, disorientation, poor attention, lack of judgment and insight, disturbance of volition, poor impulse control, preoccupation and active social avoidance. PANSS General Psychopathology Subscale Score ranges from 16 (absence of symptoms) to 112 (extremely severe symptoms). Endpoint is defined as study day 356 or the last post-baseline assessment if early discontinuation.
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=27 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=58 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
n=31 Participants
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
n=28 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
n=61 Participants
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
n=10 Participants
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint
|
-12.4 units on a scale
Standard Deviation 8.33
|
-5.4 units on a scale
Standard Deviation 7.35
|
0.2 units on a scale
Standard Deviation 5.73
|
-9.4 units on a scale
Standard Deviation 7.43
|
-3.9 units on a scale
Standard Deviation 7.37
|
-2.5 units on a scale
Standard Deviation 2.88
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline and Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
The Clinician Global Impression - Severity (CGI-S) score is a 7-point clinician-rated scale for assessing the global severity of the illness. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Negative change from baseline scores indicate improvement in the severity of illness whereas higher scores mean a worse outcome. Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=27 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=58 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
n=31 Participants
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
n=28 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
n=61 Participants
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
n=10 Participants
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
Clinician Global Impression - Severity (CGI-S) Total Score Mean Change From Baseline to Endpoint
|
-1.3 units on a scale
Standard Deviation 1.02
|
-0.5 units on a scale
Standard Deviation 0.94
|
0.0 units on a scale
Standard Deviation 0.53
|
-1.0 units on a scale
Standard Deviation 0.88
|
-0.3 units on a scale
Standard Deviation 0.80
|
-0.1 units on a scale
Standard Deviation 0.32
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
The Clinical Global Impression - Improvement (CGI-I) is a single 7-point rating score total improvement, regardless of whether or not the change it is due entirely to drug treatment. Raters select one response based on the following question, "Compared to your patient's condition at the beginning of treatment, how much has your patient changed?" Scores are: 1, Very much improved; 2, Much improved; 3, Minimally improved; 4, No change; 5, Minimally worse; 6, Much worse; or 7, Very much worse. Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=27 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=58 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
n=31 Participants
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
n=28 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
n=61 Participants
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
n=10 Participants
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
Clinician Global Impression - Improvement (CGI-I) Score
|
2.3 score on a scale
Standard Deviation 1.18
|
2.9 score on a scale
Standard Deviation 1.14
|
3.7 score on a scale
Standard Deviation 1.09
|
2.4 score on a scale
Standard Deviation 0.92
|
2.9 score on a scale
Standard Deviation 1.24
|
3.1 score on a scale
Standard Deviation 1.10
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
Overall response was defined as either PANSS total score ≥ 30% decrease from baseline, or CGI-I score of 2 (much improved) or 1 (very much improved). Endpoint is defined as study day 365 or the last post-baseline assessment if early discontinuation.
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=27 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=58 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
n=31 Participants
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
n=28 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
n=61 Participants
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
n=10 Participants
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
Overall Response Rate at Endpoint
|
74.1 percentage of participants
Interval 53.7 to 88.9
|
44.8 percentage of participants
Interval 31.7 to 58.5
|
9.7 percentage of participants
Interval 2.0 to 25.8
|
64.3 percentage of participants
Interval 44.1 to 81.4
|
45.9 percentage of participants
Interval 33.1 to 59.2
|
20.0 percentage of participants
Interval 2.5 to 55.6
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study.
Relapse was defined as either increase from baseline in PANSS total score ≥30% or rehospitalization for psychotic symptoms or use of adjunctive antipsychotic medication after stabilization.
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=27 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=58 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
n=31 Participants
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
n=28 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
n=61 Participants
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
n=10 Participants
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
Relapse Rate
|
11.1 percentage of participants
Interval 2.4 to 29.2
|
10.3 percentage of participants
Interval 3.9 to 21.2
|
12.9 percentage of participants
Interval 3.6 to 29.8
|
0 percentage of participants
Interval 0.0 to 0.0
|
13.1 percentage of participants
Interval 5.8 to 24.2
|
20.0 percentage of participants
Interval 2.5 to 55.6
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study. Safety data were pooled in two comparison groups (Risperidone ISM 75 mg and Risperidone ISM 100 mg) because the sample size increased and therefore the precision around the estimates.
An Adverse event (AE) is any symptom, physical sign, syndrome, or disease that either emerges during the study (from the informed consent form signature) or, if present at screening, worsens during the study, regardless of the suspected cause of the event. The treatment-emergent AEs (TEAEs) are defined as events that are newly occurring or worsening from the time of the first dose of the intramuscular study drug.
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=116 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=99 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
Patients With Treatment Emergent Adverse Events (TEAEs)
Patients with at least one TEAE
|
81 Participants
|
59 Participants
|
—
|
—
|
—
|
—
|
|
Patients With Treatment Emergent Adverse Events (TEAEs)
Patients with at least one treatment-related TEAE
|
43 Participants
|
41 Participants
|
—
|
—
|
—
|
—
|
|
Patients With Treatment Emergent Adverse Events (TEAEs)
Patients with at least one serious TEAE
|
6 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
|
Patients With Treatment Emergent Adverse Events (TEAEs)
Patients with at least one TEAE leading to treatment discontinuation
|
7 Participants
|
8 Participants
|
—
|
—
|
—
|
—
|
|
Patients With Treatment Emergent Adverse Events (TEAEs)
Patients with at least one TEAE leading to death
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study. Safety data were pooled in two comparison groups (Risperidone ISM 75 mg and Risperidone ISM 100 mg) because the sample size increased and therefore the precision around the estimates.
TEAEs which resulted in permanent study drug discontinuation
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=116 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=99 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
TEAEs Leading to Study Drug Discontinuation
Libido decreased
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
|
TEAEs Leading to Study Drug Discontinuation
Akathisia
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
|
TEAEs Leading to Study Drug Discontinuation
Diabetes mellitus
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
|
TEAEs Leading to Study Drug Discontinuation
Extrapyramidal disorder
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
|
TEAEs Leading to Study Drug Discontinuation
Gynaecomastia
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
|
TEAEs Leading to Study Drug Discontinuation
Hepatic Steatosis
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
|
TEAEs Leading to Study Drug Discontinuation
Hepatocellular injury
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
|
TEAEs Leading to Study Drug Discontinuation
Schizophrenia
|
2 Participants
|
5 Participants
|
—
|
—
|
—
|
—
|
|
TEAEs Leading to Study Drug Discontinuation
Suicidal ideation
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
|
TEAEs Leading to Study Drug Discontinuation
Weight increased
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to Day 365 (or the last post-baseline assessment)Population: The analysis was undertaken on the population of patients who received at least one dose of study drug during the OLE study. Safety data were pooled in two comparison groups (Risperidone ISM 75 mg and Risperidone ISM 100 mg) because the sample size increased and therefore the precision around the estimates.
An Adverse event (AE) is any symptom, physical sign, syndrome, or disease that either emerges during the study (from the informed consent form signature) or, if present at screening, worsens during the study, regardless of the suspected cause of the event. The treatment-emergent AEs (TEAEs) are defined as events that are newly occurring or worsening from the time of the first dose of the intramuscular study drug. The temporal relationship of the AE with the investigational medicinal product makes causality possible, and the AE cannot be due to another cause such as other drugs, a surgical intervention, or an underlying disease
Outcome measures
| Measure |
Rollover Placebo/Risperidone ISM 75 mg
n=116 Participants
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
Rollover Risperidone ISM 75mg/Risperidone ISM 75mg
n=99 Participants
Patients assigned to this arm were those who had been receiving 75 mg of Risperidone ISM in the previous double-blind study were randomly assigned to receive Risperidone ISM 75 mg during the OLE study.
|
De Novo/Risperidone ISM 75mg
Patients assigned to this arm were de novo participants who received 75 mg of Risperidone ISM during the OLE study. Their previous oral risperidone dose was 4 mg/day.
|
Rollover Placebo/Risperidone ISM 100 mg
Patients assigned to this arm were those who had been receiving placebo in the previous double-blind study and they were randomly assigned to receive either Risperidone ISM 100 mg during the OLE study.
|
Rollover Risperidone ISM 100 mg/Risperidone ISM 100 mg
Patients assigned to this arm were those who had been receiving 100 mg of Risperidone ISM in the previous double-blind study and they were randomly assigned to receive Risperidone ISM 100 mg during the OLE study.
|
De Novo/Risperidone ISM 100 mg
Patients assigned to this arm were de novo participants who received 100 mg of Risperidone ISM® in the OLE study. Their previous oral risperidon was more than 4 mg/day to a maximum of 6 mg/day
|
|---|---|---|---|---|---|---|
|
Patients With Treatment-related TEAEs
Akathisia
|
4 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
|
Patients With Treatment-related TEAEs
Asthenia
|
7 Participants
|
4 Participants
|
—
|
—
|
—
|
—
|
|
Patients With Treatment-related TEAEs
Dizziness
|
3 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
|
Patients With Treatment-related TEAEs
Headache
|
16 Participants
|
10 Participants
|
—
|
—
|
—
|
—
|
|
Patients With Treatment-related TEAEs
Hyperprolactinemia
|
11 Participants
|
10 Participants
|
—
|
—
|
—
|
—
|
|
Patients With Treatment-related TEAEs
Insomnia
|
6 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
|
Patients With Treatment-related TEAEs
Weight increased
|
6 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
Adverse Events
Risperidone ISM 75 mg
Serious events: 6 serious events
Other events: 81 other events
Deaths: 1 deaths
Risperidone ISM 100 mg
Serious events: 5 serious events
Other events: 59 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Risperidone ISM 75 mg
n=116 participants at risk
Patients assigned to this arm will received 75 mg of Risperidone ISM during the open label extension.
Risperidone ISM 75 mg: Monthly intramuscular (IM) injection in the gluteal or deltoid muscle.
Safety data were pooled in two comparison groups (Risperidone ISM 75 mg and Risperidone ISM 100 mg) because the sample size increased and therefore the precision around the estimates.
|
Risperidone ISM 100 mg
n=99 participants at risk
Patients assigned to this arm will received 100 mg of Risperidone ISM during the open label extension.
Risperidone ISM 100 mg: Monthly IM injection in the gluteal or deltoid muscle.
Safety data were pooled in two comparison groups (Risperidone ISM 75 mg and Risperidone ISM 100 mg) because the sample size increased and therefore the precision around the estimates.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.86%
1/116 • Number of events 1 • Day 1 to week 52
|
0.00%
0/99 • Day 1 to week 52
|
|
Psychiatric disorders
Completed suicide
|
0.86%
1/116 • Number of events 1 • Day 1 to week 52
|
0.00%
0/99 • Day 1 to week 52
|
|
Psychiatric disorders
Insomnia
|
0.86%
1/116 • Number of events 1 • Day 1 to week 52
|
0.00%
0/99 • Day 1 to week 52
|
|
Psychiatric disorders
Schizophrenia
|
2.6%
3/116 • Number of events 4 • Day 1 to week 52
|
4.0%
4/99 • Number of events 4 • Day 1 to week 52
|
|
Psychiatric disorders
Suicidal ideation
|
0.86%
1/116 • Number of events 1 • Day 1 to week 52
|
0.00%
0/99 • Day 1 to week 52
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/116 • Day 1 to week 52
|
1.0%
1/99 • Number of events 1 • Day 1 to week 52
|
Other adverse events
| Measure |
Risperidone ISM 75 mg
n=116 participants at risk
Patients assigned to this arm will received 75 mg of Risperidone ISM during the open label extension.
Risperidone ISM 75 mg: Monthly intramuscular (IM) injection in the gluteal or deltoid muscle.
Safety data were pooled in two comparison groups (Risperidone ISM 75 mg and Risperidone ISM 100 mg) because the sample size increased and therefore the precision around the estimates.
|
Risperidone ISM 100 mg
n=99 participants at risk
Patients assigned to this arm will received 100 mg of Risperidone ISM during the open label extension.
Risperidone ISM 100 mg: Monthly IM injection in the gluteal or deltoid muscle.
Safety data were pooled in two comparison groups (Risperidone ISM 75 mg and Risperidone ISM 100 mg) because the sample size increased and therefore the precision around the estimates.
|
|---|---|---|
|
Nervous system disorders
Headache
|
20.7%
24/116 • Number of events 46 • Day 1 to week 52
|
18.2%
18/99 • Number of events 29 • Day 1 to week 52
|
|
Psychiatric disorders
Anxiety
|
2.6%
3/116 • Number of events 3 • Day 1 to week 52
|
4.0%
4/99 • Number of events 4 • Day 1 to week 52
|
|
Psychiatric disorders
Insomnia
|
11.2%
13/116 • Number of events 16 • Day 1 to week 52
|
3.0%
3/99 • Number of events 6 • Day 1 to week 52
|
|
Psychiatric disorders
Schizophrenia
|
4.3%
5/116 • Number of events 9 • Day 1 to week 52
|
5.1%
5/99 • Number of events 7 • Day 1 to week 52
|
|
Endocrine disorders
Hyperprolactinaemia
|
9.5%
11/116 • Number of events 13 • Day 1 to week 52
|
10.1%
10/99 • Number of events 10 • Day 1 to week 52
|
|
Gastrointestinal disorders
Diarrhoea
|
4.3%
5/116 • Number of events 5 • Day 1 to week 52
|
1.0%
1/99 • Number of events 2 • Day 1 to week 52
|
|
Gastrointestinal disorders
Toothache
|
3.4%
4/116 • Number of events 8 • Day 1 to week 52
|
3.0%
3/99 • Number of events 3 • Day 1 to week 52
|
|
General disorders
Asthenia
|
6.0%
7/116 • Number of events 8 • Day 1 to week 52
|
4.0%
4/99 • Number of events 5 • Day 1 to week 52
|
|
Infections and infestations
Nasopharyngitis
|
11.2%
13/116 • Number of events 15 • Day 1 to week 52
|
9.1%
9/99 • Number of events 9 • Day 1 to week 52
|
|
Investigations
Alanine aminotransferase increased
|
1.7%
2/116 • Number of events 2 • Day 1 to week 52
|
3.0%
3/99 • Number of events 4 • Day 1 to week 52
|
|
Investigations
Weight increased
|
6.9%
8/116 • Number of events 9 • Day 1 to week 52
|
4.0%
4/99 • Number of events 4 • Day 1 to week 52
|
|
Nervous system disorders
Akathisia
|
3.4%
4/116 • Number of events 4 • Day 1 to week 52
|
4.0%
4/99 • Number of events 5 • Day 1 to week 52
|
|
Nervous system disorders
Dizziness
|
3.4%
4/116 • Number of events 4 • Day 1 to week 52
|
3.0%
3/99 • Number of events 3 • Day 1 to week 52
|
Additional Information
Director of Medical Department
Laboratorios Farmacéuticos Rovi, S.A.
Phone: 91 375 62 30
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor does not object to publication by the Institution of the results of the Trial based on information collected/generated by the Institution. The Institution will provide Sponsor an opportunity to review any proposed publication before it is submitted. If the Trial is part of a multi-center trial, the Institution agress that the first publication is to be a joint publication involving all Trials sites.
- Publication restrictions are in place
Restriction type: OTHER