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

This study has been terminated.
(Inability to recruit number of planned patients)
Sponsor:
Information provided by (Responsible Party):
Janssen-Ortho Inc., Canada
ClinicalTrials.gov Identifier:
NCT00256997
First received: November 18, 2005
Last updated: November 12, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Schizophrenia
Drug: Risperidone long-acting injection (LAI)
Drug: Oral atypical Antipsychotic
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pragmatic Randomized Trial of Risperdal Consta Versus Oral Atypical Antipsychotics in Poorly Adherent Subjects With Schizophrenia in a Routine Care Setting

Resource links provided by NLM:


Further study details as provided by Janssen-Ortho Inc., Canada:

Primary Outcome Measures:
  • Percentage of Participants Who Experienced a Clinical Exacerbation From Month 3 Post-Randomization [ Time Frame: Month 3 up to Month 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Who Experienced a Clinical Exacerbation [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
    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.

  • Time to First Clinical Exacerbation [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
    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.

  • Time in Symptomatic (Having Symptoms) Remission [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Total Score at Month 24 [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Clinical Global Impression of Severity (CGI-S) [ Time Frame: Baseline and End of Study (Month 24 or Early Withdrawal [EW]) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Clinical Global Impression of Change (CGI-C) [ Time Frame: End of Study (Month 24 or Early Withdrawal [EW]) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Response to Resource Utilization Questionnaire (RUQ) [ Time Frame: Baseline up to Month 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Assessment of Quality of Life (AQoL) Score at Month 24 [ Time Frame: Baseline and Month 24 ] [ Designated as safety issue: No ]
    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)".

  • Change From Baseline in Personal and Social Performance Scale (PSP) Total Score at Month 24 [ Time Frame: Baseline and End of Study (Month 24 or Early Termination [ET]) ] [ Designated as safety issue: No ]
    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).


Enrollment: 167
Study Start Date: January 2006
Study Completion Date: April 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00256997

  Show 44 Study Locations
Sponsors and Collaborators
Janssen-Ortho Inc., Canada
Investigators
Study Director: Janssen Inc. Clinical Trial Janssen Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen-Ortho Inc., Canada
ClinicalTrials.gov Identifier: NCT00256997     History of Changes
Other Study ID Numbers: CR006016, RISSCH4055
Study First Received: November 18, 2005
Results First Received: February 27, 2013
Last Updated: November 12, 2013
Health Authority: Canada: Institutional Review Board
Canada: Health Canada

Keywords provided by Janssen-Ortho Inc., Canada:
Schizophrenia
Risperidone
Risperdal Consta

Additional relevant MeSH terms:
Schizophrenia
Mental Disorders
Schizophrenia and Disorders with Psychotic Features
Antipsychotic Agents
Risperidone
Central Nervous System Agents
Central Nervous System Depressants
Dopamine Agents
Dopamine Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Serotonin Agents
Serotonin Antagonists
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on October 23, 2014