Parallel Group, Multiple Dose Pharmacokinetics Study of Five Antipsychotic Medications in Psychiatric Participants

Schizophrenia Clinical Trial

Official title:

Open-Label Pharmacokinetic Study to Evaluate the Steady-State Venous and Capillary Plasma Concentrations of Five Antipsychotics: Aripiprazole, Olanzapine, Paliperidone, Quetiapine and Risperidone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02087579
• Other study ID #: CR103695
• Secondary ID: 2013-005289-20IN
• Status: Completed
• Phase: Phase 1
• First received: February 17, 2014
• Last updated: October 28, 2015
• Start date: February 2014
• Est. completion date: December 2014

Study information

• Verified date: October 2015
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: National Health Surveillance AgencyCzech Republic: State Institute for Drug ControlPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSpain: Agencia Española de Medicamentos y Productos SanitariosRomania: National Medicines AgencyBulgaria: Bulgarian Drug AgencyUnited States: Institutional Review BoardGermany: Ethics CommissionGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to gather information about the steady-state plasma concentrations of aripiprazole, olanzapine, quetiapine and their relevant metabolites, at various dose levels and at different time points after dosing. In addition, comparison of capillary drug concentrations vs. venous drug concentrations will be performed for aripiprazole, olanzapine, paliperidone, quetiapine, risperidone and their relevant metabolites.

Description:

This is an open-label (physicians and participants know the identity of the assigned treatment), parallel-group, multiple-dose, multicenter study to assess pharmacokinetics (what the body does to the medication) of five antipsychotics (APS) drugs: aripiprazole, olanzapine, paliperidone, quetiapine and risperidone in psychiatric participants who are receiving stable doses of these drugs for the treatment of their disease.

Pharmacokinetics data will be generated from venous and fingerstick-based capillary plasma concentrations of the drugs and their metabolites. The total number of enrolled participants in this study will be at least 265. Seventy-five participants will be enrolled for the aripiprazole, olanzapine and quetiapine cohorts (groups) each, and 20 participants will be enrolled for the paliperidone and risperidone cohorts each. In aripiprazole, olanzapine and quetiapine cohorts there will be two subgroups. Subgroup one, 20 participants for fingerstick capillary + venous blood sampling and subgroup two, 55 participants for only venous sampling. Paliperidone and risperidone cohorts will be subjected only to capillary + venous blood sampling.

The study will consist of a screening phase (within 21 days before Day 1) followed by a 3-day observation phase (Day 1 to Day 3). Participants will be admitted to the study center in the evening of Day -1 and will remain in the study center until discharged on Day 3 after completion of the last study-related procedure. During the observation phase, the administration of the prior antipsychotic medication will continue at a participant's usual dose and dosing schedule, under direct observation of the study staff. There will be no modification of the participant's medication during the study. Safety will be evaluated throughout the study and a mandatory pharmacogenomic blood sample will be collected for analysis of genes that may influence exposure of the APS studied.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 305
• Est. completion date: December 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Must be clinically stable as per the investigator's judgment (no suicidal behavior or current significant suicidal judgment based on C-SSRS rating scale)

• No hospitalization for exacerbation of psychiatric symptoms during 3 months before screening

• Receiving treatment with aripiprazole, olanzapine, paliperidone, quetiapine or risperidone, or their combination before the study

• Must have body mass index between 17 and 40 kg/m2 (inclusive), and body weight not less than 47 kg

• Except for the indication for which the antipsychotic treatment is given, generally healthy with no clinically significant or unstable medical problems

• Must be able to give informed consent

Exclusion Criteria:

• Clinically significant abnormal physical examination, vital signs or 12-lead ECG at screening as determined by the investigator

• Administering of strong inhibitors or inducers of CYP3A4, CYP2D6 enzymes, like fluoxetine

• History of or current clinically significant (particularly unstable) medical illness other than the indication

• Donated blood or blood products or had substantial loss of blood (more than 450 mL) within 3 months before Day -1

• Lack of 6 suitable puncture sites for capillary blood draws

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Bipolar Disorder
• Depression
• Depressive Disorder
• Disease
• Mental Disorders
• Psychotic Disorders
• Schizophrenia

Intervention

Drug:
• Aripiprazole, oral formulation
Aripiprazole tablets will be administered orally (by mouth), at no dose restriction, as per the locally approved label indications.
• Olanzapine, oral formulation
Olanzapine tablets will be administered orally, at no dose restriction as per the locally approved label indications.
• Paliperidone, oral formulation
Paliperidone prolonged-release/extended-release (XR) formulation tablets will be administered orally, at no dose restriction, as per the locally approved label indications.
• Paliperidone, LAI
Paliperidone long-acting injectable (LAI) i.e., paliperidone palmitate injections, will be administered per the locally approved label indications.
• Quetiapine, oral formulation
Quetiapine immediate-release (IR) formulation or extended-release (XR) formulation tablets will be administered orally, at no dose restriction, as per the locally approved label indications.
• Risperidone, oral formulation
Risperidone tablets will be administered orally, at no dose restriction, as per the locally approved label indications.
• Risperidone, LAI
Risperidone LAI injections will be administered will be administered per the locally approved label indications.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Bulgaria,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aripiprazole concentration in venous and capillary plasma	Venous blood samples will be collected at 8 scheduled time points after dosing and compared to fingerstick-based capillary blood samples collected at 6 scheduled time points after dosing.	14 time points over 3 days postdose	No
Primary	Paliperidone concentration in venous and capillary plasma		14 time points over 3 days postdose	No
Primary	Olanzapine concentration in venous and capillary plasma		14 time points over 3 days postdose	No
Primary	Quetiapine concentration in venous and capillary plasma		14 time points over 3 days postdose	No
Primary	Risperidone concentration in venous and capillary plasma		14 time points over 3 days postdose	No
Secondary	Number of participants with an adverse event as a measure of safety		Participants will be followed for the duration of hospital stay, an expected average of 3 days	Yes

External Links

•   Open-Label Pharmacokinetic Study to Evaluate the Steady-State Venous and Capillary Plasma Concentrations of 5 Antipsychotics: Aripiprazole, Olanzapine, Paliperidone, Quetiapine and Risperidone