Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Risperidone in Situ Microparticle (ISM)® in Patients With Acute Schizophrenia (NCT NCT03160521)

Last Updated: 2022-02-22

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 indicate improvements in symptoms whereas higher scores mean a worse outcome. Endpoint is defined as study day 85 or the last post-baseline assessment if early discontinuation.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

438 participants

Primary outcome timeframe

Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

Results posted on

2022-02-22

Participant Flow

Participant milestones

Participant milestones
Measure	Risperidone in Situ Microparticle (ISM) 75 mg Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly IM intramuscular (IM) injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly IM injection in the gluteal or deltoid muscle.	Placebo Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly IM injection in the gluteal or deltoid muscle.
Overall Study STARTED	144	146	147
Overall Study COMPLETED	107	95	88
Overall Study NOT COMPLETED	37	51	59

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of Risperidone in Situ Microparticle (ISM)® in Patients With Acute Schizophrenia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Risperidone ISM 75 mg n=129 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=129 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo n=132 Participants Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Total n=390 Participants Total of all reporting groups
Age, Continuous	42.6 years STANDARD_DEVIATION 10.63 • n=5 Participants	42.6 years STANDARD_DEVIATION 11.14 • n=7 Participants	40.0 years STANDARD_DEVIATION 11.35 • n=5 Participants	41.7 years STANDARD_DEVIATION 11.08 • n=4 Participants
Sex: Female, Male Female	41 Participants n=5 Participants	45 Participants n=7 Participants	47 Participants n=5 Participants	133 Participants n=4 Participants
Sex: Female, Male Male	88 Participants n=5 Participants	84 Participants n=7 Participants	85 Participants n=5 Participants	257 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants	19 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	123 Participants n=5 Participants	126 Participants n=7 Participants	122 Participants n=5 Participants	371 Participants n=4 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
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
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 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
Race (NIH/OMB) Black or African American	58 Participants n=5 Participants	63 Participants n=7 Participants	59 Participants n=5 Participants	180 Participants n=4 Participants
Race (NIH/OMB) White	69 Participants n=5 Participants	65 Participants n=7 Participants	71 Participants n=5 Participants	205 Participants n=4 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
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United States	72 participants n=5 Participants	72 participants n=7 Participants	76 participants n=5 Participants	220 participants n=4 Participants
Region of Enrollment Ukraine	57 participants n=5 Participants	57 participants n=7 Participants	56 participants n=5 Participants	170 participants n=4 Participants
Body Mass Index (BMI)	27.77 Kg/m^2 STANDARD_DEVIATION 5.226 • n=5 Participants	28.26 Kg/m^2 STANDARD_DEVIATION 5.268 • n=7 Participants	28.19 Kg/m^2 STANDARD_DEVIATION 4.715 • n=5 Participants	28.07 Kg/m^2 STANDARD_DEVIATION 5.065 • n=4 Participants
Years since Schizophrenia Diagnosis	16.1 years STANDARD_DEVIATION 10.67 • n=5 Participants	15.7 years STANDARD_DEVIATION 10.43 • n=7 Participants	14.3 years STANDARD_DEVIATION 9.74 • n=5 Participants	15.4 years STANDARD_DEVIATION 10.29 • n=4 Participants
Time since Acute Exacerbation or relapse (weeks)	3 days STANDARD_DEVIATION 1.95 • n=5 Participants	3 days STANDARD_DEVIATION 3.67 • n=7 Participants	3 days STANDARD_DEVIATION 1.65 • n=5 Participants	3 days STANDARD_DEVIATION 2.55 • n=4 Participants

PRIMARY outcome

Timeframe: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

Population: The efficacy analysis was performed on the modified Intent-to-treat (mITT) population containing all randomized patients who received ≥1 dose of study drug with a baseline measurement and ≥1 post-baseline evaluation for the PANSS, and for whom blinding was not potentially compromised owing to a one-off error in the interactive web response system (IWRS) used for randomized treatment assignment.

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=129 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=129 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo n=132 Participants Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
PANSS Total Score Mean Change From Baseline to Endpoint	-24.6 units on a scale Standard Error 1.51	-24.7 units on a scale Standard Error 1.54	-11.0 units on a scale Standard Error 1.56

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

Population: The efficacy analysis was performed on the mITT population containing all randomized patients who received ≥1 dose of study drug with a baseline measurement and ≥1 post-baseline evaluation for the PANSS, and for whom blinding was not potentially compromised owing to a one-off error in the interactive web response system (IWRS) used for randomized treatment assignment.

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 85 or the last post-baseline assessment if early discontinuation.

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=129 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=129 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo n=132 Participants Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
CGI-S Total Score Mean Change From Baseline to Endpoint	-1.3 units on a scale Standard Error 0.09	-1.3 units on a scale Standard Error 0.09	-0.6 units on a scale Standard Error 0.09

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

The Clinical Global Impression - Improvement (CGI-I) Score consists of a single 7-point rating score total improvement, regardless of whether or not the change it is due entirely to drug treatment. 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 85 or the last post-baseline double-blind assessment if early discontinuation.

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=129 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=129 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo n=132 Participants Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
CGI-I Score Mean at Endpoint	2.5 units on a scale Standard Error 0.10	2.5 units on a scale Standard Error 0.10	3.3 units on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Day 85 or the last post-baseline assessment

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 85 or the last post-baseline assessment if early discontinuation.

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=129 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=129 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo n=132 Participants Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
Overall Response Rate at Endpoint	59.7 percentage of participants Interval 50.7 to 68.2	54.3 percentage of participants Interval 45.3 to 63.1	20.5 percentage of participants Interval 13.9 to 28.3

SECONDARY outcome

Timeframe: Day 85 or the last post-baseline assessment

The definition of Positive and Negative Syndrome Scale (PANSS) response was a decrease from baseline in PANSS total score of ≥ 30% (improvement of symptoms). Endpoint is defined as study day 85 or the last post-baseline double-blind assessment if early discontinuation.

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=129 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=129 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo n=132 Participants Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
PANSS Response Rate at Endpoint	41.9 percentage of participants Interval 33.2 to 50.9	34.9 percentage of participants Interval 26.7 to 43.8	9.1 percentage of participants Interval 4.8 to 15.3

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

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 85 or the last post-baseline assessment if early discontinuation.

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=129 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=129 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo n=132 Participants Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
PANSS Positive Subscale Mean Change From Baseline to Endpoint	-8.0 units on a scale Standard Error 0.49	-8.7 units on a scale Standard Error 0.50	-4.1 units on a scale Standard Error 0.50

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

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 85 or the last post-baseline assessment if early discontinuation.

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=129 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=129 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo n=132 Participants Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
PANSS Negative Subscale Mean Change From Baseline to Endpoint	-3.8 units on a scale Standard Error 0.38	-3.7 units on a scale Standard Error 0.39	-1.7 units on a scale Standard Error 0.40

SECONDARY outcome

Timeframe: Day 1 (Baseline) and Day 85 (or the last post-baseline assessment)

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 85 or the last post-baseline assessment if early discontinuation.

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=129 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=129 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo n=132 Participants Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
PANSS General Psychopathology Subscale Mean Change From Baseline to Endpoint	-12.8 units on a scale Standard Error 0.79	-12.4 units on a scale Standard Error 0.81	-5.6 units on a scale Standard Error 0.82

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 (Baseline), Days 29, 57 and 85 (or the last post-baseline assessment)

Population: The intent-to-treat (ITT) population (used for analyses of this outcome) consisted of all randomized patients who received at least 1 dose of study drug with a baseline measurement and ≥ 1 post-baseline evaluation of the PANSS. Data for both Risperidone ISM doses (75 mg and 100 mg) were pooled because this study was not powered to detect differences between doses at this endpoint and pooling this two arms the sample size increase and therefore the precision around the estimates.

Personal and Social Performance Scale (PSP) total score mean change from baseline at each post-baseline assessment time point. The PSP is a 100-point single-item rating scale that is based on 4 domains: family and social functioning, self-care, work and socially useful activities, and disturbing and aggressive behaviors. Each domain is rated in 6 degrees of severity (absent, mild, manifest, marked, severe, very severe). On the PSP scale, higher scores indicate better social functioning: 71-100 indicates mild to no functional impairment; 31-70 varying degrees of disability and 1-30, minimal functioning needing intense support and/or supervision. Participants with a PSP total score of 71 to 100 were considered to have mild functional difficulty. Scores of 31 to 70 represented varying degrees of disability (31 to 70) and ratings of 1 to 30 indicated minimal functioning that required intense support and/or supervision.

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=288 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=145 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
PSP Total Score From Baseline at Each Post-baseline Assessment Time Point Baseline	49.93 score on a scale Interval 49.0 to 51.0	50.46 score on a scale Interval 49.0 to 52.0	—
PSP Total Score From Baseline at Each Post-baseline Assessment Time Point Study Day 29	59.03 score on a scale Interval 58.0 to 60.0	55.37 score on a scale Interval 54.0 to 57.0	—
PSP Total Score From Baseline at Each Post-baseline Assessment Time Point Study Day 57	61.33 score on a scale Interval 60.0 to 63.0	57.07 score on a scale Interval 55.0 to 59.0	—
PSP Total Score From Baseline at Each Post-baseline Assessment Time Point Study Day 85	60.60 score on a scale Interval 59.0 to 62.0	54.54 score on a scale Interval 53.0 to 56.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 (Baseline), Days 29, 57 and 85 or the last post-baseline assessment

20-item Subjective Well-Being Under Neuroleptics Treatment Scale (SWN-20) total score mean change from baseline at each post-baseline assessment time point. The SWN is a 38-item instrument to measure subjective effects of neuroleptic medications in patients with schizophrenia and consists of 20 positive statements and 18 negative statements. The short form of the SWN, the 20-item SWN-20, was developed in order to allow for quick assessment of subjective side effects in a clinical setting. Like in the original SWN, with the SWN-20 the patient is asked to rate well-being items that have been identified as related to antipsychotic treatment on a 6-point scale ranging from "Not at all" to "Very much." The SWN-20 is scored on a scale ranging from 20 to 120, with higher scores indicating better health-related quality of life (HRQL). The SWN-20 contains five 4-item subscales: mental functioning, self-control, emotional regulation, physical functioning, and social integration. Eac

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=288 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=145 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
SWN-20 Total Score From Baseline at Each Post-baseline Assessment Time Point Baseline	80.86 score on a scale Interval 79.0 to 83.0	80.28 score on a scale Interval 78.0 to 83.0	—
SWN-20 Total Score From Baseline at Each Post-baseline Assessment Time Point Day 29	86.90 score on a scale Interval 85.0 to 89.0	83.23 score on a scale Interval 81.0 to 86.0	—
SWN-20 Total Score From Baseline at Each Post-baseline Assessment Time Point Day 57	88.26 score on a scale Interval 87.0 to 90.0	86.32 score on a scale Interval 83.0 to 89.0	—
SWN-20 Total Score From Baseline at Each Post-baseline Assessment Time Point Day 85	89.14 score on a scale Interval 88.0 to 91.0	85.50 score on a scale Interval 83.0 to 88.0	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 3 and Day 29 after Dose 1, 2 and 3

Population: Pharmacokinetic (PK) population included patients in the safety population who have at least 1 measurement plasma concentration value.

Plasma PK Parameters of Risperidone Active Moiety Cmax values are estimated and based on the plasma level of Day 3 for each dosing Interval; Cmin are the trough levels of Day 29, which is at the end of each dosing Interval;

Outcome measures

Outcome measures
Measure	Risperidone ISM 75 mg n=144 Participants Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=146 Participants Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
Plasma PK Parameters Dose 1/Estimated Cmax/Day 3	27.61 ng/mL Standard Deviation 19.992	32.00 ng/mL Standard Deviation 16.802	—
Plasma PK Parameters Dose 1/Estimated Cmin/Day 29	19.21 ng/mL Standard Deviation 13.076	26.71 ng/mL Standard Deviation 14.960	—
Plasma PK Parameters Dose 2/Estimated Cmax/Day 3	38.95 ng/mL Standard Deviation 22.381	53.44 ng/mL Standard Deviation 23.840	—
Plasma PK Parameters Dose 2/Estimated Cmin/Day 29	17.46 ng/mL Standard Deviation 13.418	27.23 ng/mL Standard Deviation 14.070	—
Plasma PK Parameters Dose 3/Estimated Cmax/Day 3	37.16 ng/mL Standard Deviation 19.504	50.09 ng/mL Standard Deviation 22.242	—
Plasma PK Parameters Dose 3/Estimated Cmin/Day 29	20.16 ng/mL Standard Deviation 16.847	26.14 ng/mL Standard Deviation 16.343	—

Adverse Events

Risperidone ISM 75 mg

Serious events: 2 serious events

Other events: 101 other events

Deaths: 0 deaths

Risperidone ISM 100 mg

Serious events: 5 serious events

Other events: 119 other events

Deaths: 0 deaths

Placebo

Serious events: 5 serious events

Other events: 48 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Risperidone ISM 75 mg n=144 participants at risk Patients assigned to this arm will received 75 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 75 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Risperidone ISM 100 mg n=146 participants at risk Patients assigned to this arm will received 100 mg of Risperidone ISM during double-blind treatment period. Risperidone ISM 100 mg: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.	Placebo n=147 participants at risk Patients assigned to this arm will received placebo of Risperidone ISM during double-blind treatment period. Placebo of Risperidone ISM: Monthly (once every 4 weeks) IM injection in the gluteal or deltoid muscle.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/144 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.00% 0/146 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.68% 1/147 • Number of events 1 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.
Infections and infestations Appendicitis	0.69% 1/144 • Number of events 1 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.00% 0/146 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.00% 0/147 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.
Infections and infestations Pneumonia	0.00% 0/144 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.00% 0/146 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.68% 1/147 • Number of events 1 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.
Infections and infestations Skin infection	0.00% 0/144 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.68% 1/146 • Number of events 1 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.00% 0/147 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.
Injury, poisoning and procedural complications Fall	0.00% 0/144 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.68% 1/146 • Number of events 1 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.00% 0/147 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/144 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.68% 1/146 • Number of events 1 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.00% 0/147 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.
Psychiatric disorders Agitation	0.00% 0/144 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.68% 1/146 • Number of events 1 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	0.00% 0/147 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.
Psychiatric disorders Schizophrenia	0.69% 1/144 • Number of events 1 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	1.4% 2/146 • Number of events 2 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.	2.7% 4/147 • Number of events 4 • Adverse event data were collected in all visits of the study, from the patient's signature of informed consent form through the end of study for each subject: Screening visit, Baseline (Day 1), Day 3, 4, 8, 15, 22, 29, 31, 43, 57, 59, 71, 85 and follow-up visit (Day 99). The analysis was performed in the Safety Population, which includes all patients who received at least 1 dose of the study drug. 437 patients were included in the safety population.

Other adverse events

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