Clozapine/Paliperidone Versus Clozapine/Placebo in Resistant Schizophrenia

Schizophrenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01279213
• Other study ID #: 109
• Status: Completed
• Phase: Phase 4
• First received: January 11, 2011
• Last updated: January 18, 2011
• Start date: January 2009
• Est. completion date: December 2009

Study information

• Verified date: July 2009
• Source: Universidad Nacional de Rosario
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Human Research Bioethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: December 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 50 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Disease
• Mental Disorders
• Psychotic Disorder
• Psychotic Disorders
• Schizophrenia
• Schizophrenic Disorders

Intervention

Drug:
• paliperidone clozapine
dose 3 to 12 mg paliperidone ER daily during 12 weeks

Locations

Country	Name	City	State
Argentina	Faculty of Psychology	Rosario	Santa Fe

Sponsors (1)

Lead Sponsor	Collaborator
Universidad Nacional de Rosario

Country where clinical trial is conducted

Argentina, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	bprs	improvement in scores total BPRS	12 weeks	No
Secondary	cgs	improvement in CGS	12 weeks	No