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

Official Title: “Pragmatic Randomized Trial of Risperdal� CONSTA� (Risperidone) 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 patients with a history of being poorly compliant with taking their medication.

This is a randomized, open-label, parallel group, multi-country and multi-centre study of Risperdal long-acting formulation versus oral atypical antipsychotics in subjects with a DSM-IV TR diagnosis of schizophrenia currently being treated with oral antipsychotic medication. The primary objective of this trial is to determine whether Risperdal long-acting formulation provides improved effectiveness over a 2-year period, measured by the proportion of subjects who experience a clinical exacerbation, as compared to oral atypical antipsychotics prescribed in a routine care setting for the treatment of subjects with schizophrenia. Subjects will be randomized to an oral atypical antipsychotic (risperidone, olanzapine, quetiapine, and where commercially available, aripiprazole and amisulpride) or to Risperdal long-acting formulation. For Risperdal long-acting formulation subjects, study medication will be administered by intramuscular injection every 2 weeks at doses of 25, 37.5 or 50 mg. Oral supplementation with the current oral atypical antipsychotic is required for the first 3 weeks following the initial injection and dose increases. Dose increases can be made as per product labeling. The primary measure of effectiveness is the reduction in the proportion of subjects experiencing a clinical exacerbation after being in the study for 3 months. Additional measures of effectiveness include: symptom improvement on the Positive and Negative Syndrome Scale for schizophrenia (PANSS) and Clinical Global Impression (CGI) - S/C; use of health care resources as assessed by Resource Utilization Questionnaire (RUQ) and changes in quality of life, assessed using Assessment of Quality of Life (AQoL) questionnaire; time to first clinical exacerbation; the number of clinical exacerbations calculated at 2 time points: occurring 12 weeks post-randomization and the entire trial duration; the proportion of clinical exacerbations for the entire trial period; the evaluation of symptomatic remission over time; and the Personal and Social Performance Scale (PSP). Safety assessments include the incidence of adverse events throughout the study, AIMS, laboratory tests, vital signs, weight, waist and hip circumference and physical examination.

Addendum: In the sentence starting "Oral supplementation with the current…" the words "or conventional neuroleptic" were removed. The latest version of the protocol (amendment #2) does not allow for the use of conventional neuroleptics as oral supplementation. Oral atypical antipsychotic (risperidone, olanzapine, quetiapine, aripiprazole or amisulpride, dosage according to product labeling) or risperidone, long-acting formulation (25, 37.5 or 50 mg) administered by intramuscular injection every 2 weeks, for the 2-year study. Oral supplementation with the current oral atypical antipsychotic is required for the first 3 weeks following the initial injection and dose increases.

Addendum: removed conventional neuroleptic. See 4b for details.

Intervention(s) in this Clinical Trial

• Drug: Oral atypical anitpsychotics
  • As per local label. Medication administered daily for 24 months.
• Drug: Risperidone long acting injection
  • 25-50 mg i.m. injection every 2 weeks for 24 months

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 001
  • Risperidone long acting injection 25-50 mg i.m. injection every 2 weeks for 24 months
• Active Comparator: 002
  • Oral atypical anitpsychotics As per local label. Medication administered daily for 24 months.

Primary Measures

• The proportion of subjects experiencing a clinical intensification of schizophrenia symptoms after being in the study for 3 months.
  • Time Frame: 24 months post-randomization
    Safety Issue?: No

Secondary Measures

• PANSS, CGI-S and CGI-C, RUQ, AQoL, PSP, evaluation of symptomatic remission over time, proportion of clinical intensification of symptoms during the trial, time to intensification of symptoms and the number of incidences of intensification of symptoms
  • Time Frame: 24 months post-randomization
    Safety Issue?: Yes

Inclusion Criteria:

• Diagnosis of schizophrenia as per DSM-IV
• have had at least 2 hospitalizations or 2 clinical worsening of symptoms over the past 2 years due the patient suspected of being poorly compliant with taking their medication
• is currently receiving treatment with an antipsychotic per local labeling, and has a history in the last 5 years of a satisfactory response (minimum of 6 weeks) to oral antipsychotics (excluding clozapine)
• otherwise healthy, as confirmed by physical exam, vital signs, and laboratory testing: female subjects 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:

• Subjects with a primary DSM-IV TR Axis I diagnosis other than schizophrenia
• previously treated or currently on clozapine
• have a serious, unstable and untreated medical illnesses, such as vascular or cardiovascular disease, history of liver or kidney disease, significant cardiac, pulmonary, gastrointestinal, endocrine, neurological or metabolic disturbances
• at significant risk of suicide or violence at study start
• evidence of alcohol or medication abuse or dependence.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Janssen-Ortho Inc., Canada Industry

Overall Clinical Trial Officials and Contacts

Janssen-Ortho Inc. Clinical Trial Study Director Janssen-Ortho Inc., Canada  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00256997

Study ID Number: CR006016

ClinicalTrials.gov Identifier: NCT00256997

Health Authority: United States: Institutional Review Board

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