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

Phase 1
Completed
Conditions
Psychotic Disorders
Schizophrenia
Bipolar Disorder
Depressive Disorder
Interventions
Drug: Aripiprazole, oral formulation
Drug: Olanzapine, oral formulation
Drug: Paliperidone, oral formulation
Drug: Quetiapine, oral formulation
Drug: Risperidone, oral formulation
Drug: Paliperidone, LAI
Drug: Risperidone, LAI
Registration Number
NCT02087579
Lead Sponsor
Janssen Research & Development, LLC
Brief 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.

Detailed 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 & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
305
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort A: AripiprazoleAripiprazole, oral formulationAdministration of oral formulation will continue at a participant's usual dose and dosing schedule.
Cohort B: OlanzapineOlanzapine, oral formulationAdministration of oral formulation will continue at a participant's usual dose and dosing schedule.
Cohort C: PaliperidonePaliperidone, oral formulationAdministration of prolonged-release (extended-release) tablets or long-acting injectables (LAI) will continue at a participant's usual dose and dosing schedule.
Cohort C: PaliperidonePaliperidone, LAIAdministration of prolonged-release (extended-release) tablets or long-acting injectables (LAI) will continue at a participant's usual dose and dosing schedule.
Cohort D: QuetiapineQuetiapine, oral formulationAdministration of oral formulation will continue at a participant's usual dose and dosing schedule.
Cohort E: RisperidoneRisperidone, oral formulationAdministration of oral formulation or LAI will continue at a participant's usual dose and dosing schedule.
Cohort E: RisperidoneRisperidone, LAIAdministration of oral formulation or LAI will continue at a participant's usual dose and dosing schedule.
Primary Outcome Measures
NameTimeMethod
Olanzapine concentration in venous and capillary plasma14 time points over 3 days postdose
Aripiprazole concentration in venous and capillary plasma14 time points over 3 days postdose

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.

Paliperidone concentration in venous and capillary plasma14 time points over 3 days postdose
Risperidone concentration in venous and capillary plasma14 time points over 3 days postdose
Quetiapine concentration in venous and capillary plasma14 time points over 3 days postdose
Secondary Outcome Measures
NameTimeMethod
Number of participants with an adverse event as a measure of safetyParticipants will be followed for the duration of hospital stay, an expected average of 3 days
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