Evaluation of the Strategies of Switching Schizophrenia Patients to Aripiprazole From Other Antipsychotic Agents

Schizoaffective Disorder Clinical Trial

Official title:

Evaluation of the Strategies of Switching Schizophrenia Patients to Aripiprazole From Other Antipsychotic Agents: Combination of Pharmacogenomics and Therapeutic Drug Monitoring

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00545467
• Other study ID #: 200705030M
• Status: Completed
• Phase: Phase 4
• First received: October 15, 2007
• Last updated: May 16, 2012
• Start date: August 2007
• Est. completion date: July 2009

Study information

• Verified date: January 2012
• Source: National Taiwan University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether moderately ill Asian schizophrenic patients can be switched from their previous antipsychotic medication to aripiprazole with minimal adverse clinical consequences, and elucidate both pharmacokinetic and pharmacodynamic factors associated with clinical efficacy of aripiprazole.

Description:

Aripiprazole (commercial name abilify) is the first commercially available drug with dopamine partial agonist effects approved for the treatment of schizophrenia and bipolar disorder since 2002 in the U.S. It reduces negative symptoms of schizophrenia efficiently and has a markedly lower incidence of extrapyramidal symptoms and tardive dyskinesia. However, the process of switching other antipsychotic agents to aripiprazole can result in a re-emergence or worsening of psychosis, along with unpleasant side effects such as insomnia, nausea, vomiting, anxiety and agitation. On the basis of a prior study demonstrating the efficacy and safety of aripiprazole in Taiwan population, we hence propose to apply a combined use of pharmacogenomics and therapeutic drug monitoring in the evaluation of the strategies of switching stable schizophrenia patients to aripiprazole from other antipsychotic agents.

We will evaluate their cytochrome P450 background along with other potential candidate genes of schizophrenia. This 2-year proposal will examine the relative efficacy, safety and tolerability of two different strategies for switching stable inpatients/outpatients from prior antipsychotic monotherapy to aripiprazole 15 mg/day monotherapy using two different strategies:

1. Fast tapering of the previous medication within 1 week after initiating aripiprazole for 2 weeks.

2. Slow tapering of the previous medication within 4 weeks after initiating aripiprazole for 2 weeks.

A total of 200 stable schizophrenia patients will be randomized with open label to two strategies.

We expect to achieve the following results:

1. Developing a protocol that has high probability of switching successfully schizophrenia patients to aripiprazole, which is effective in treatment refractory cases and has a markedly lower incidence of severe side effects, from other antipsychotics.

2. Elucidate both pharmacokinetic and pharmacodynamic factors associated with clinical efficacy of aripiprazole.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: July 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Men and non-lactating, non-pregnant women who are aged 18 to 65 years

• primary diagnosis of DSM-IV schizophrenia or schizoaffective disorder

• taking a stabilized dose of a single oral antipsychotic for at least 1 month prior to study entry

• cannot have been hospitalized for an exacerbation of schizophrenia or schizoaffective disorder for at least 2 months

Exclusion Criteria:

• having other psychiatric disorders

• hospitalizing for acute exacerbation of patients' condition within 2 months

• having taken a selective serotonin reuptake inhibitor (SSRI) within 4 weeks of screening

• a first episode of schizophrenia or schizoaffective disorder

• a clinically significant neurological abnormality other than tardive dyskinesia or EPS

• current diagnosis of psychoactive substance dependence or a historical drug or alcohol abuse within 1 month before the beginning of the study

• treatment with an investigational drug within 4 weeks prior to randomization

• requiring to take medication that inhibits the microsomal enzyme CYP2D6 or inhibits or acts as a substrate for CYP3A4

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• DSM-IV Schizophrenia
• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Drug:
• Aripiprazole
Aripiprazole will be given as a fixed does, 15 mg/day, orally throughout 8 weeks in the 2 arms.

Locations

Country	Name	City	State
Taiwan	Department of Psychiatry, National Taiwan University Hospital	Taipei

Sponsors (3)

Lead Sponsor	Collaborator
National Taiwan University Hospital	National Science Council, Taiwan, Taoyuan Psychiatric Center, Ministry of Health and Welfare, Executive Yuan, R.O.C. Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment efficacy was assessed using PNASS, Clinical Global Impression (CGI) Scale, and EPS rating scales		on days 0, 7, 14, 28, 56	No
Secondary	HPLC analysis Genotyping		on days 0, 14, 56	No