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

Pragmatic Randomized Trial of Risperdal Consta Versus Oral Atypical Antipsychotics in Poorly Adherent Subjects With Schizophrenia in a Routine Care Setting

The purpose of this study is to evaluate risperidone long-acting injection (an antipsychotic medication) versus oral antipsychotics in schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) participants with a history of being poorly compliant with taking their medication.

Study Overview

• Status: Terminated
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Risperidone long-acting injection (LAI); Drug: Oral atypical Antipsychotic

Detailed Description

This is a Phase 4, an open-label (all people know the identity of the intervention), multi-country and multi-centric (conducted in more than one center) study of risperidone long-acting formulation versus oral (having to do with the mouth) atypical antipsychotics in participants with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text revision ( DSM-IV TR) diagnosis of schizophrenia currently being treated with oral antipsychotic medication. The duration of this study will be 2 years. All the eligible participants will be randomly assigned to an oral atypical antipsychotic (risperidone, olanzapine, quetiapine, and where commercially available, aripiprazole and amisulpride) or to risperidone long-acting formulation. For risperidone long-acting formulation participants, study medication will be administered by intramuscular (into the muscle) injection every 2 weeks at doses of 25, 37.5 or 50 milligram (mg). Oral supplementation with the current oral atypical antipsychotic is required for the first 3 weeks following the initial injection and dose increase. Dose increase can be made as per product labeling. The primary measure of effectiveness is the reduction in the percentage of participants experiencing a clinical exacerbation after being in the study for 3 months. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Dandenong, Australia
  • Frankston, Australia
  • Mt Claremont, Australia
  • Newcastle, Australia
  • Southport, Australia
• Canada
  • Montreal, Canada
  • Quebec, Canada
  • Saint John, Canada
  • Alberta
    • Calgary, Alberta, Canada
  • New Brunswick
    • Bathurst, New Brunswick, Canada
  • Nova Scotia
    • Kentville, Nova Scotia, Canada
    • Sydney, Nova Scotia, Canada
  • Ontario
    • Kingston, Ontario, Canada
    • Mississauga, Ontario, Canada
    • Sudbury, Ontario, Canada
  • Quebec
    • Beauport, Quebec, Canada
    • Montreal, Quebec, Canada
    • Saint-Georges, Quebec, Canada
  • Saskatchewan
    • Battleford, Saskatchewan, Canada
    • Prince Albert, Saskatchewan, Canada
• Ireland
  • Co.Mayo, Ireland
  • Dublin, Ireland
  • Mullingar, Ireland
• United Kingdom
  • Birmingham, United Kingdom
  • Boston, United Kingdom
  • Bristol, United Kingdom
  • Burnley, United Kingdom
  • Darwen, United Kingdom
  • Devon, United Kingdom
  • Grantham, United Kingdom
  • Leicester, United Kingdom
  • Lincoln, United Kingdom
  • London, United Kingdom
  • Morpeth, United Kingdom
  • Newcastle Upon Tyne, United Kingdom
  • Northampton, United Kingdom
  • Nottingham, United Kingdom
  • Preston, United Kingdom
  • Stamford, United Kingdom
  • Stockton-Upon-Tees, United Kingdom
  • Swansea, United Kingdom
  • Teignmouth, United Kingdom
  • Wallsend, United Kingdom
  • Weston Super Mare, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: - Diagnosis of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) as per Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text revision (DSM-IV TR)- Have had at least 2 hospitalizations or 2 clinical worsening of symptoms, over the past 2 years because of deteriorating adherence - Is currently receiving treatment with an antipsychotic per local product label guidelines, and has a history in the last 5 years of a satisfactory response (minimum of 6 weeks) to oral antipsychotics (excluding clozapine) - On monotherapy antipsychotic treatment as per local product label guidelines, at Baseline -Female participants must be surgically sterile, or practicing an effective method of birth control before entry and throughout the study, and have a negative urine pregnancy test at screening before study entry Exclusion Criteria: - Participants with a primary DSM-IV TR Axis I diagnosis other than schizophrenia - Female participants who are currently pregnant or breastfeeding or planning a pregnancy within 2 years of trial start - Have a serious, unstable and untreated medical illnesses, such as vascular or cardiovascular disease, history of liver or kidney disease, significant cardiac (having to do with the heart), pulmonary (having to do with the lungs), gastrointestinal, endocrine, neurological (pertaining to the nervous system) or metabolic disturbances - At significant risk of suicide or violence at study start - Evidence of substance dependence (except for nicotine and caffeine dependence) according to DSM-IV TR criteria diagnosed in the last month prior to entry

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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 will be administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic will also be administered in the first 3 weeks following the dose increase. Duration of treatment will be 24 months.	Drug: 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 will be administered every 2 weeks as per Investigator's discretion. An oral atypical antipsychotic will also be administered in the first 3 weeks following the dose increase. Duration of treatment will be 24 months.
Active Comparator: Oral atypical Antipsychotic; Oral atypical antipsychotic will be administered as per local label practice for 24 months. Participants will be switched to another atypical oral therapy as per Investigator's discretion.	Drug: Oral atypical Antipsychotic; Oral atypical antipsychotic will be administered as per local label practice for 24 months. Participants will be switched to another atypical oral therapy as per Investigator's discretion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced a Clinical Exacerbation From Month 3 Post-Randomization	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.	Month 3 up to Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced a Clinical Exacerbation	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.	Baseline up to Month 24
Time to First Clinical Exacerbation	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.	Baseline up to Month 24
Time in Symptomatic (Having Symptoms) Remission	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.	Baseline up to Month 24
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Month 24	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.	Baseline and Month 24
Number of Participants With Clinical Global Impression of Severity (CGI-S)	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.	Baseline and End of Study (Month 24 or Early Withdrawal [EW])
Number of Participants With Clinical Global Impression of Change (CGI-C)	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.	End of Study (Month 24 or Early Withdrawal [EW])
Number of Participants With Response to Resource Utilization Questionnaire (RUQ)	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.	Baseline up to Month 24
Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24	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)".	Baseline and Month 24
Change From Baseline in Personal and Social Performance Scale (PSP) Total Score at Month 24	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).	Baseline and End of Study (Month 24 or Early Termination [ET])

Collaborators and Investigators

• Sponsor: Janssen-Ortho Inc., Canada

Publications and helpful links

Helpful Links

• Pragmatic randomized trial of Risperdal Consta versus oral atypical antipsychotics in poorly adherent subjects with schizophrenia in a routine care setting.

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: November 18, 2005
• First Submitted That Met QC Criteria: November 18, 2005
• First Posted (Estimate): November 22, 2005

Study Record Updates

• Last Update Posted (Estimate): December 5, 2013
• Last Update Submitted That Met QC Criteria: November 12, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Schizophrenia; Risperidone; Risperdal Consta
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone; Antipsychotic Agents
• Other Study ID Numbers: CR006016; RISSCH4055