Long-acting Injectable Risperidone in Patients With Schizophrenia After an Acute Episode

Early Versus Late Initiation of Treatment With Risperdal Consta in Subjects With Schizophrenia After an Acute Episode

The primary objective of this randomized trial was to investigate whether early initiation of treatment with Risperdal Consta after an acute episode was not inferior to the routine approach (oral treatment for 12 weeks followed by treatment with Risperdal Consta). .

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: early initiation of treatment with Risperdal Consta; Drug: routine initiation of treatment with Risperdal Consta

Detailed Description

Although many schizophrenia patients currently take oral antipsychotic medications, it is estimated that up to 75% of them have difficulty adhering to the daily oral regiment. Long-acting injectable formulations may eliminate the need for daily medication and enhance patient compliance with the treatment regimen. Traditionally, patients experiencing an episode of schizophrenia are first treated with oral medications until they are stabilized, and then injectable long-acting formulations are given. This is an open, multicenter, randomized Phase IV trial in patients after an acute episode of schizophrenia. Patients will be in the trial for 6 months. One treatment group will receive injections starting at baseline (early initiation); the other group will start with treatment as usual at baseline and begin injections at Week 12 (late initiation). Assessment of effectiveness include Positive And Negative Syndrome Scale (PANSS), in order to measure symptoms of schizophrenia; Clinical Global Impression - Severity (CGI-S), measuring overall severity of illness; Global Assessment of Functioning (GAF), assessesing overall psychological, social, and occupational functioning; and Quality of Life Questionnaire SF-12, measuring overall health status. Safety evaluations include the Extrapyramidal Symptoms Rating Scale (ESRS), incidence of adverse events throughout the study, and vital signs (pulse, blood pressure). The study hypothesis is that early initiation of long-acting risperidone injections is not inferior to late initiation as measured by changes in PANSS total score from baseline through endpoint (after 6 months). Risperidone, long-acting formulation for intramuscular injections (25 to 50 mg (maximum)), given every 14 days through 6 months, starting at baseline or Month 3. Treatment as usual for 3 months for late initiation group

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
  • Glostrup, Denmark
  • Hjørring, Denmark
  • Kolding N/A, Denmark
• Finland
  • Helsinki, Finland
  • Vantaa, Finland
• France
  • Bar Le Duc, France
  • Beaupuy, France
  • Clermont Ferrand, France
  • Colmar, France
  • La Seyne Sur Mer, France
  • Mont St Martin, France
• Greece
  • Athens, Greece
  • Chania, Greece
  • Thessalonikis, Greece
  • Tripoli, Greece
• Israel
  • Bat-Yam, Israel
  • Pardesia, Israel
  • Petah-Tikva, Israel
• Norway
  • Levanger, Norway
• Slovenia
  • Ljubljana, Slovenia
• Sweden
  • Danderyd, Sweden
  • Göteborg, Sweden
  • Huddinge N/A, Sweden
  • Stockholm N/A, Sweden
  • Trollhättan, Sweden
• Switzerland
  • Oetwil Am See, Switzerland
  • St Urban, Switzerland
  • Zuerich, Switzerland
• United Kingdom
  • London, United Kingdom
  • Norfolk, 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 by criteria of Diagnostic and Statistical Manual of Mental Diseases, Fourth Edition (DSM-IV)
• acute episode of schizophrenia within 2 weeks of study entry
• o subjects currently not treated or treated with oral antipsychotics or short-acting injectable antipsychotics (zuclopenthixol acutard is allowed) at doses not exceeding the registered dose
• Positive And Negative Syndrome Scale (PANSS) score >=80
• Clinical Global Impression - Severity (CGI-S) score >=5

Exclusion Criteria:

• DSM-IV axis I diagnosis other than schizophrenia
• known hypersensitivity or lack of response to risperidone
• pregnant or nursing females, or those without adequate contraception
• alcohol or drug abuse or dependence 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: 001; early initiation of treatment with Risperdal Consta 25 mg to 50 mg Risperdal Consta intrmuscular injection every 14 days starting at baseline. Treatment with oral antipsychotics or risperidone will continue 21 days after the first injection of Risperdal Consta. This treatment will then be tapered off within the next 7 days.	Drug: early initiation of treatment with Risperdal Consta; 25 mg to 50 mg Risperdal Consta intrmuscular injection every 14 days starting at baseline. Treatment with oral antipsychotics or risperidone will continue 21 days after the first injection of Risperdal Consta. This treatment will then be tapered off within the next 7 days.
Active Comparator: 002; routine initiation of treatment with Risperdal Consta 25 mg to 50 mg Risperdal Consta intrmuscular injection every 14 days starting at week 12. Treatment with oral antipsychotics or risperidone will continue 21 days after the first injection of Risperdal Consta. This treatment will then be tapered off within the next 7 days.	Drug: routine initiation of treatment with Risperdal Consta; 25 mg to 50 mg Risperdal Consta intrmuscular injection every 14 days starting at week 12. Treatment with oral antipsychotics or risperidone will continue 21 days after the first injection of Risperdal Consta. This treatment will then be tapered off within the next 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Positive And Negative Syndrome Scale (PANSS) Total Score From Baseline to Endpoint	The PANSS is a specific scale for the measurement of the symptoms of schizophrenia. Symptoms of schizophrenia will be assessed using the 30-item PANSS scale. Each item of the scale is to be scored on a scale of 1 (absent) to 7 (extreme).The total score can range from 30 to 210.	at baseline and Week 26 or at premature discontinuation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in PANSS Total Score at Week 6	The PANSS is a specific scale for the measurement of the symptoms of schizophrenia. Symptoms of schizophrenia will be assessed using the 30-item PANSS scale. Each item of the scale is to be scored on a scale of 1 (absent) to 7 (extreme). The total score can range from 30 to 210.	at baseline and Week 6.
Change From Baseline in PANSS Total Score at Week 12	The PANSS is a specific scale for the measurement of the symptoms of schizophrenia. Symptoms of schizophrenia will be assessed using the 30-item PANSS scale. Each item of the scale is to be scored on a scale of 1 (absent) to 7 (extreme). The total score can range from 30 to 210.	at baseline and Week 12.
Change From Baseline to Endpoint in Clinical Global Impression - Severity (CGI-S)	The CGI-S rating scale is used to rate the severity of a subject's psychotic condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). This scale permits a global evaluation of the subject's condition at a given time.	at baseline and endpoint (week 26 or at premature discontinuation).
Change From Baseline to Endpoint in Global Assessment of Functioning (GAF)	Overall psychological, social, and occupational functioning is rated on a scale of mental health-illness from 1 being the worst functioning to 100 being the best. Impairment in functioning due to physical (or environmental) limitations must not be included in the rating.	at baseline and endpoint (week 26 or at premature discontinuation).
Change From Baseline to Endpoint in Quality of Life Questionnaire SF-12	Short Form Health Survey: A generic dual-ie, mental and physical health-scale measure of quality of life. This is a 12-item subset of the SF-36 survey that measures the same 8 domains of health. As a brief, reliable measure of overall health status, the SF-12 is the instrument of choice in large population health surveys and has been used extensively as a screening tool. SF-12 will be filled in by the patient. The scores range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.	at baseline, Weeks 6, 12, and endpoint (week 26 or at premature discontinuation).

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutica N.V., Belgium

Study record dates

Study Major Dates

• Study Start: November 1, 2005
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 14, 2005
• First Posted (Estimate): September 22, 2005

Study Record Updates

• Last Update Posted (Estimate): July 19, 2013
• Last Update Submitted That Met QC Criteria: July 12, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Schizophrenia; intramuscular injection; antipsychotic agents; long-acting risperidone
• 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; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Risperidone
• Other Study ID Numbers: CR002257

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No