Trial Outcomes & Findings for A Study of Risperidone Long-Acting Injection Versus Oral Antipsychotics in Schizophrenia Participants With a History of Being Poorly Compliant With Taking Their Medication (NCT NCT00256997)

Last Updated: 2013-12-05

Results Overview

Clinical exacerbation is defined as hospitalization because of participant's schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, delusions, hallucinations, and self withdrawal) or requiring change from current antipsychotic or initiation of adjunctive antipsychotic, 2-point worsening in Clinical Global Impression of Severity (CGI-S) or emergency room visit, deliberate self-injury, emergence of clinically significant suicidal ideation, utilization of treatment team services, violent behavior, requiring an increase in dose of existing antipsychotic as a result of poor symptom control.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

167 participants

Primary outcome timeframe

Month 3 up to Month 24

Results posted on

2013-12-05

Participant Flow

Participant milestones

Participant milestones
Measure	Risperidone Long-Acting Injection (LAI) Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Overall Study STARTED	81	86
Overall Study Treated	79	86
Overall Study COMPLETED	33	31
Overall Study NOT COMPLETED	48	55

Reasons for withdrawal

Reasons for withdrawal
Measure	Risperidone Long-Acting Injection (LAI) Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Overall Study Protocol Violation	1	4
Overall Study Lack of Efficacy	1	4
Overall Study Death	2	0
Overall Study Adverse Event	4	0
Overall Study Lost to Follow-up	3	5
Overall Study Withdrawal by Subject	13	3
Overall Study Started but not treated	2	0
Overall Study Other	5	8
Overall Study End of Study (As Per Sponsor)	12	24
Overall Study Participant Non-compliant	3	6
Overall Study Investigator Withdrew Participant	2	1

Baseline Characteristics

A Study of Risperidone Long-Acting Injection Versus Oral Antipsychotics in Schizophrenia Participants With a History of Being Poorly Compliant With Taking Their Medication

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Risperidone Long-Acting Injection (LAI) n=79 Participants Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic n=86 Participants Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.	Total n=165 Participants Total of all reporting groups
Age Continuous	37.4 Years STANDARD_DEVIATION 12.46 • n=5 Participants	38.9 Years STANDARD_DEVIATION 10.9 • n=7 Participants	38.2 Years STANDARD_DEVIATION 11.67 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	23 Participants n=7 Participants	46 Participants n=5 Participants
Sex: Female, Male Male	56 Participants n=5 Participants	63 Participants n=7 Participants	119 Participants n=5 Participants

PRIMARY outcome

Timeframe: Month 3 up to Month 24

Population: Intent-to-treat (ITT) population included all participants who received medication with at least one post-baseline effectiveness measure. This study was stopped due to futility; care must be exercised in any interpretation of utilization of these data.

Outcome measures

Outcome measures
Measure	Risperidone Long-Acting Injection (LAI) n=79 Participants Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic n=86 Participants Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Percentage of Participants Who Experienced a Clinical Exacerbation From Month 3 Post-Randomization	48.1 Percentage of participants	43.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Month 24

Population: ITT population included all participants who received medication with at least one post-baseline effectiveness measure. This study was stopped due to futility; care must be exercised in any interpretation of utilization of these data.

Clinical exacerbation is defined as hospitalization because of participant's schizophrenia or requiring change from current antipsychotic or initiation of an adjunctive antipsychotic, 2-point worsening in CGI-S or emergency room visit, deliberate self-injury, emergence of clinically significant suicidal ideation, utilization of treatment team services, violent behavior, requiring an increase in dose of existing antipsychotic as a result of poor symptom control.

Outcome measures

Outcome measures
Measure	Risperidone Long-Acting Injection (LAI) n=79 Participants Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic n=86 Participants Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Percentage of Participants Who Experienced a Clinical Exacerbation	54.4 Percentage of participants	54.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline up to Month 24

Population: ITT population included all participants who received medication with at least one post-baseline effectiveness measure. Here, 'N' signifies number of participants evaluated for this outcome measure. This study was stopped due to futility; care must be exercised in any interpretation of utilization of these data.

Time to first clinical exacerbation was calculated over the entire trial duration wherein clinical exacerbation is defined as hospitalization because of participant's schizophrenia or requiring change from current antipsychotic or initiation of an adjunctive antipsychotic, 2-point worsening in CGI-S or emergency room visit, deliberate self-injury, emergence of clinically significant suicidal ideation, utilization of treatment team services, violent behavior, requiring an increase in dose of existing antipsychotic as a result of poor symptom control.

Outcome measures

Outcome measures
Measure	Risperidone Long-Acting Injection (LAI) n=78 Participants Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic n=85 Participants Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Time to First Clinical Exacerbation	10.4 Months Standard Error 0.80	11.2 Months Standard Error 0.93

SECONDARY outcome

Timeframe: Baseline up to Month 24

Population: Data for this outcome was not computed as it was not defined in terms of the formula for calculation and thus was not included in analysis plan.

Time in symptomatic (having symptoms) remission for participants on risperidone was compared with those on oral atypical medication and was calculated over the entire trial duration.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT population. Here, 'N' signifies number of participants evaluated for this outcome measure. 'n' signifies number of participants who were evaluated for this outcome measure at given timepoint. This study was stopped due to futility; care must be exercised in any interpretation of utilization of these data.

The PANSS is a 30-item scale designed to assess various symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210, higher scores indicate worsening.

Outcome measures

Outcome measures
Measure	Risperidone Long-Acting Injection (LAI) n=79 Participants Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic n=85 Participants Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Month 24 Baseline (n=79, 85)	77.6 Units on a scale Standard Deviation 17.24	76.5 Units on a scale Standard Deviation 17.83
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Month 24 Change at Month 24: Total score (n=67, 67)	-9.6 Units on a scale Standard Deviation 19.80	-12.4 Units on a scale Standard Deviation 21.83

SECONDARY outcome

Timeframe: Baseline and End of Study (Month 24 or Early Withdrawal [EW])

The CGI-S rating scale is used to rate the severity of a patient's psychotic condition on a 7-point scale. It is rated as follows: 1=Normal, not at all ill, 2=Borderline mentally ill, 3=Mildly ill, 4=Moderately ill, 5=Markedly ill, 6=Severely ill, and 7=Among the most extremely ill. Higher scores indicate worsening.

Outcome measures

Outcome measures
Measure	Risperidone Long-Acting Injection (LAI) n=79 Participants Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic n=85 Participants Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Number of Participants With Clinical Global Impression of Severity (CGI-S) Baseline: Mild or better (n=79, 85)	18 participants	26 participants
Number of Participants With Clinical Global Impression of Severity (CGI-S) Baseline: Moderate, marked and severe (n=79, 85)	61 participants	59 participants
Number of Participants With Clinical Global Impression of Severity (CGI-S) Month 24/EW: Mild or better (n=67, 68)	36 participants	39 participants
Number of Participants With Clinical Global Impression of Severity (CGI-S) Month 24/EW:Moderate,marked and severe (n=67, 68)	31 participants	29 participants

SECONDARY outcome

Timeframe: End of Study (Month 24 or Early Withdrawal [EW])

The CGI-C is a assessment of change in global clinical status, defined as a sense of well-being and ability to function in daily activities. CGI-C scores range from 1 (very much improved) through to 7 (very much worse). Higher scores indicate worsening.

Outcome measures

Outcome measures
Measure	Risperidone Long-Acting Injection (LAI) n=67 Participants Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic n=68 Participants Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Number of Participants With Clinical Global Impression of Change (CGI-C) Month 24/EW:At least minimally improved(n= 67,68)	48 Participants	38 Participants
Number of Participants With Clinical Global Impression of Change (CGI-C) Month 24/EW: No change or worse (n=67,68)	19 Participants	30 Participants

SECONDARY outcome

Timeframe: Baseline up to Month 24

This questionnaire included questions asked to participants about any hospitalizations, visits to the emergency room or any other psychiatric treatment received in the previous month. Also the participants and/or primary health care contact or caregiver (or other modality to obtain accurate information) were telephoned on a monthly basis (1 month post Visit 2 through to end of study \[Visit 6, Month 24\]) by a member of the investigational staff and the resource utilization assessment was conducted over the phone.

Outcome measures

Outcome measures
Measure	Risperidone Long-Acting Injection (LAI) n=79 Participants Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic n=86 Participants Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Outpatient clinic (total reports)	31 Participants	36 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Suicide/crisis services (total reports)	13 Participants	13 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Emergency room visits (total reports)	32 Participants	29 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Hospital admissions (total reports)	42 Participants	32 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Family doctor visits (total reports)	59 Participants	58 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Psychologist doctor visit (total reports)	14 Participants	13 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Social worker (total reports)	43 Participants	44 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Occupational therapist (total reports)	28 Participants	30 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Phychiatric day care (total reports)	19 Participants	13 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Phychiatrist (total reports)	74 Participants	78 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Visit by a home care nurse (total reports)	15 Participants	8 Participants
Number of Participants With Response to Resource Utilization Questionnaire (RUQ) Psychiatric nurse (total reports)	62 Participants	58 Participants

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: ITT population. Here 'N' signifies number of participants evaluated for this outcome measure and 'n' signifies number of participants who were evaluated for this outcome measure at given timepoint. This study was stopped due to futility; care must be exercised in any interpretation of utilization of these data.

AQoL is defined as an Australian-developed participant delivered quality of life (QoL) instrument consisting of 15-questions in 5 scales measuring illness, independence, social relationships, physical senses and psychological well-being. Each of the 5 scales is calculated based on the answers to 3 questions. Each question is given an answer dependent utility score (0 \[worst\] to 1 \[best\] and then these scores are combined using a multiplicative model to get the normalized scale score value, each scale ranging between 0.0 (representing death) and 1.0 (representing full health). The scores for independent living, social relationships, physical senses and psychological well-being are combined to obtain the QoL utility score which refers to the "value" of a health state to the respondent where the lower boundary is -0.04 (representing QoL state worse than death), 0.00 (death equivalent QoL state) and to 1.00 (best possible QoL state)".

Outcome measures

Outcome measures
Measure	Risperidone Long-Acting Injection (LAI) n=79 Participants Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic n=84 Participants Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 Baseline: Illness score (n=79,84)	0.396 Units on a scale Standard Deviation 0.2496	0.359 Units on a scale Standard Deviation 0.2549
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 Change at Month 24: Illness score (n=64,67)	0.091 Units on a scale Standard Deviation 0.3086	0.035 Units on a scale Standard Deviation 0.3101
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 Baseline: Daily activity score(n=79,83)	0.811 Units on a scale Standard Deviation 0.2312	0.872 Units on a scale Standard Deviation 0.2156
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 Change at Month 24: Daily activity score(n=64,67)	0.051 Units on a scale Standard Deviation 0.2370	-0.038 Units on a scale Standard Deviation 0.2283
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 Baseline: Social score (n=79,83)	0.608 Units on a scale Standard Deviation 0.2926	0.613 Units on a scale Standard Deviation 0.3117
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 Change at Month 24: Social score (n=64,66)	0.060 Units on a scale Standard Deviation 0.3143	0.025 Units on a scale Standard Deviation 0.3474
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 Baseline: Physical score (n=79,83)	0.872 Units on a scale Standard Deviation 0.1437	0.916 Units on a scale Standard Deviation 0.1022
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 Change at Month 24: Physical score (n=64,67)	0.065 Units on a scale Standard Deviation 0.1581	0.020 Units on a scale Standard Deviation 0.0919
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 Baseline: Psychological score (n=79,83)	0.863 Units on a scale Standard Deviation 0.1469	0.863 Units on a scale Standard Deviation 0.1595
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 Change at Month 24: Psychological score (64,67)	0.015 Units on a scale Standard Deviation 0.1677	0.023 Units on a scale Standard Deviation 0.01527

SECONDARY outcome

Timeframe: Baseline and End of Study (Month 24 or Early Termination [ET])

The PSP is 100-point validated clinician-rated scale that assesses degree of difficulty in 4 areas of functioning: socially useful activities, personal and social relationships, self-care, disturbing and aggressive behaviors rated on 6-point scale (1=absent to 6=very severe).Total transformed score from 1 to 100 is generated from raw score based on clinical interpretation of scores generated in 4 areas of functioning, with higher transformed score indicating better function. Total score is divided into 3 levels: 71-100 (mild difficulty); 31-70 (marked difficulty) and 1-30 (severe difficulty).

Outcome measures

Outcome measures
Measure	Risperidone Long-Acting Injection (LAI) n=79 Participants Risperidone LAI 25 milligram (mg), 37.5 mg or 50 mg intramuscular (injection of a substance into a muscle) injection was administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic was also administered in the first 3 weeks following the dose increase. Duration of treatment was 24 months.	Oral Atypical Antipsychotic n=84 Participants Oral atypical antipsychotic was administered as per local label practice for 24 months. Participants switched to another atypical oral therapy as per Investigator's discretion.
Change From Baseline in Personal and Social Performance Scale (PSP) Total Score at Month 24 Baseline: (n=79, 84)	54.2 Units on a scale Standard Error 13.32	55.0 Units on a scale Standard Error 13.49
Change From Baseline in Personal and Social Performance Scale (PSP) Total Score at Month 24 Change at Month 24/ET: (n=67,68)	5.2 Units on a scale Standard Error 17.76	8.4 Units on a scale Standard Error 15.72

Adverse Events

Risperidone Long-Acting Injection (LAI)

Serious events: 14 serious events

Other events: 70 other events

Deaths: 0 deaths

Oral Atypical Antipsychotic

Serious events: 6 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director Medical Affairs - CNS

Janssen Inc. Toronto, Ontario, Canada

Phone: +1-416-382-5094

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60