Safety and Efficacy of Aripiprazole and Ziprasidone Among Schizophrenic Patients With Metabolic Syndrome

NCT01714011 | Completed Phase 4

• 1 other identifier: MAS001
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction: Schizophrenia is a serious mental illness. For majority of patients it is a lifetime condition,characterized by intermittent episodes of hospitalization due to relapse or acute symptom exacerbation. The nature and course of the disorder impose significant social and economic burden. Relapse is costly, with hospitalization accounting for a substantial portion of healthcare expenses. Second generation antipsychotic side effect such as metabolic syndrome and diabetes mellitus will contribute additional costs to the treatment. Many studies have since then provided convincing evidence for a high risk of diabetes and other glucose abnormalities, metabolic syndrome and mortality due to elevated cardiovascular risk in patients with schizophrenia. However many studies has shown the effectiveness and safety of aripiprazole and ziprazidone.In one of the study, aripiprazole showed improvement of negative schizophrenic symptoms by 25% and 50% of functioning level from baseline. In term of safety, antipsychotics considered to have a safer metabolic profile were amisulpride, ziprasidone and aripiprazole. Study objectives:

• To investigate the safety and efficacy of ziprazidone versus aripiprazole in the treatment of schizophrenia patients with metabolic syndrome and diabetes mellitus.
• To investigate the reversibility of metabolic syndrome and diabetes parameters following the treatment with ziprazidone versus aripiprazole. Hypotheses: \* The proportion of reversibility of metabolic syndrome and diabetes parameters is higher following the treatment of ziprazidone than aripiprazole.

Conditions

Schizophrenia

Keywords

Randomized; Controlled; Trial; Safety; Efficacy; Aripiprazole; Ziprasidone; Metabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• Tapering off of previous psychoactive medication.

  * To taper off previous psychoactive medication gradually. * The dosages of either Aripiprazole or Ziprasidone increase gradually until the patient fully switch off to those medications.

  4 weeks

Secondary Outcomes (1)

• The proportion of reversed metabolic syndrome components among schizophrenia patients after treated with either aripiprazole or ziprasidone

  6months

Other Outcomes (2)

• The least squares (LS) mean change of weight and BMI among schizophrenia patients after treated with either aripiprazole or ziprasidone.

  6 months

• Total cholesterol and LDL cholesterol among schizophrenia patients after treated with either aripiprazole or ziprasidone.

  6 months

Study Arms (2)

Ziprasidone

ACTIVE COMPARATOR

Ziprasidone is a psychotropic agent with chemical name: 5-\[2-\[4-(1,2-benzisothiazole-3-yl)-1-piperazinyl\]ethyl\]-6-chloro-1,3-dihydro-2H-indol-2-one.Ziprasidone is a potent antagonist of both serotonin 5-HT2A and dopamine D2 receptors, although its affinity for 5-HT2A receptors is about 10 times higher than for D2 receptors.

Drug: Ziprasidone

Aripiprazole

ACTIVE COMPARATOR

Aripiprazole is a psychotropic drug that is available as tablets for oral administration. Aripiprazole is 7-\[ 4-\[ 4-(2,3-dichlorophenyl)-1-piperazinyl\]butoxy\]-3-4-dihydrocarbostyril. Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5-HT2A receptors, moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha 1-adrenergic and histamine H1 receptors and moderate affinity for serotonin reuptake site (Ki = 98nM).

Drug: Aripiprazole

Interventions

Ziprasidone DRUG

Ziprasidone's activity is primarily due to the parent drug. The multiple-dose pharmacokinetics of ziprasidone are dose-proportional within the proposed clinical dose range, and ziprasidone accumulation is predictable with multiple dosing. Elimination of ziprasidone is mainly via hepatic metabolism with a mean terminal half-life of about 7 hours within the proposed clinical dose range. Steady-state concentrations are achieved within one to three days of dosing. The mean apparent systemic clearance is 7.5 mL/min/kg. Ziprasidone is unlikely to interfere with the metabolism of drugs metabolized by cytochrome P450 enzymes. Ziprasidone is well absorbed after oral administration, reaching peak plasma concentrations in 6 to 8 hours.

Also known as: Zeldox

Ziprasidone

Aripiprazole DRUG

Aripiprazole activity is presumably primarily due to the parent drug, aripiprazole and to a lesser extent, to its major metabolite, dehyrdro-aripiprazole. Steady state concentrations are attained with in 14 days of dosing. The mean elimination half lives are about 75 hours and 95 hours respectively. Elimination of aripiprazole is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP3A4. Aripiprazole is well absorbed, with peak plasma concentrations occurring within 3-5 hours; the absolute oral bioavailability of the tablet formulation is 87%. Absorption of aripiprazole is not affected by food.

Also known as: Abilify

Aripiprazole

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Schizophrenic patients
• Patients with metabolic syndrome
• Able to provide written informed consent and to comply with all study procedures

You may not qualify if:

• Patient with history of diabetes mellitus prior to the treatment of schizophrenia
• Neurological or psychiatric disorders, such as depression, bipolar illness, organic brain disease, dementia, or any diseases that require psychotropic medications
• Serious medical illnesses, including but not limited to; uncontrolled hypertension, significant heart disease (including a history of myocardial infarction, angina, mitral valve prolapse, left ventricular hypertrophy, palpitations, and arrhythmia), hepatic disease, renal disease, or any serious, potentially life-threatening or progressive medical illness that may compromise patient safety or study conduct

Sponsors & Collaborators

• University of Malaya: lead

Study Sites (1)

University Malaya Medical Centre

Kuala Lumpur, Kuala Lumpur, 59100, Malaysia

Location

MeSH Terms

Conditions

Schizophrenia; Metabolic Syndrome

Interventions

ziprasidone; Aripiprazole

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Mas Ayu Said, MBBS,MPH

  University of Malaya

  STUDY DIRECTOR

• Ahmad Hatim Sulaiman, MBBS,MPM

  University of Malaya

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2012
• First Posted: October 25, 2012
• Study Start: May 1, 2009
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: November 27, 2012

Record last verified: 2012-11

Locations

MY (1)