Clozapine/Paliperidone Versus Clozapine/Placebo in Resistant Schizophrenia

Augmentation of Clozapine With Paliperidone in the Treatment of Resistant Schizophrenia Randomized Controlled Study

augmentation of clozapine with paliperidone in the treatment of resistant schizophrenia has not been tested until now in randomized controlled trials. This combination is supposed to have therapeutic efficacy in the treatment of resistant schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizophrenic Disorders; Psychotic Disorder
• Intervention / Treatment: Drug: paliperidone clozapine

Detailed Description

This is a 12 weeks, blind study (the patient, investigator, and sponsor do not know the study drug and dosage being taken by the patient) of the safety and tolerability of flexible-dose (3 to 12mg per day), extended-release (ER) paliperidone in combination with clozapine with a diagnosis of schizophrenia. Patients who have completed study or who discontinued from that study because of lack of efficacy but completed a minimum of 21 days of the study may enter this study. This study consists of a 21-day screening and washout phase (to discontinue and "wash out" any medication not allowed in the study), and a double blind treatment phase of 12 weeks, during which all patients will take oral paliperidone ER every day and clozapine versus clozapine alone, and a post-treatment phase consisting of a follow-up visit completed 1 week after a patient has received the final dose of paliperidone ER. The study, including the screening and posttreatment phase, will last approximately 30 weeks. Screening and washout may be conducted while a patient is an outpatient. Safety will be assessed by laboratory measurements (chemistry, liver function tests, hematology, hormone, lipid assessments, prolactin [blinded], urinalysis, and urine drug screens; body weight, height, and waist circumference measurements; ECGs and the ESRS (extrapyramidal syndrome rating scale). These instruments will be used to assess extrapyramidal symptoms (EPS) and dyskinesias. Adverse events will be monitored including psychiatric adverse events of interest (worsening of psychosis, hyperprolactinemia, weight gain) that may be associated with paliperidone ER in this population. The primary aim of this study is to evaluate the long-term (12 weeks) safety and tolerability of clozapine/paliperidone ER in resistant schizophrenia. As exploratory secondary aims, the study will assess the effect of clozapine/paliperidone ER on the long-term symptoms of schizophrenia as measured by the changes in the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores, the global improvement in severity of illness as measured by the Clinical Global Impression(CGI) scale. Patients begin the study at 6.0 mg/day of oral paliperidone ER. If a higher dosage is needed, the dosage will be increased (in increments of 3 mg/day not more frequently than once every 5 days) to 12 mg/day. If the 6.0 mg/day dosage is not well tolerated, the dosage may be decreased (not more frequently than once every 5 days) to 3.0 mg/day. Patients will be dosed for up to 6 months.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Faculty of Psychology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

resistant schizophrenia failure in therapeutic response to three previous antipsychotic drugs -

Exclusion Criteria:

age upper 50 other psychiatric diagnosis head trauma neurological diseases -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: paliperidone clozapine BPRS; patients assigned to clozapine plus paliperidone controls at 6 and 12 weeks	Drug: paliperidone clozapine; dose 3 to 12 mg paliperidone ER daily during 12 weeks
Placebo Comparator: clozapine plus placebo BPRS; patients assigned to placebo plus clozapine should show less improvement	Drug: paliperidone clozapine; dose 3 to 12 mg paliperidone ER daily during 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
bprs	improvement in scores total BPRS	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cgs	improvement in CGS	12 weeks

Collaborators and Investigators

• Sponsor: Universidad Nacional de Rosario
• Investigators: Principal Investigator: daniel j serrani azcurra, MD, Faculty of Psychology

Publications and helpful links

General Publications

• Mortimer AM, Singh P, Shepherd CJ, Puthiryackal J. Clozapine for treatment-resistant schizophrenia: National Institute of Clinical Excellence (NICE) guidance in the real world. Clin Schizophr Relat Psychoses. 2010 Apr;4(1):49-55. doi: 10.3371/CSRP.4.1.4.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): October 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: January 11, 2011
• First Submitted That Met QC Criteria: January 18, 2011
• First Posted (Estimate): January 19, 2011

Study Record Updates

• Last Update Posted (Estimate): January 19, 2011
• Last Update Submitted That Met QC Criteria: January 18, 2011
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disease; Psychotic Disorders; Mental Disorders; 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 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; GABA Agents; GABA Antagonists; Paliperidone Palmitate; Clozapine
• Other Study ID Numbers: 109