Clinical trial NCT02087579: Parallel Group, Multiple Dose Pharmacokinetics Study of Five Antipsychotic Medications in Psychiatric Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psychotic Disorders
Schizophrenia
Bipolar Disorder
Depressive Disorder
Keywords: Psychotic Disorders
Schizophrenia
Bipolar Disorder
Depressive Disorder
Antipsychotics
Aripiprazole
Olanzapine
Paliperidone
Quetiapine
Risperidone
Capillary Concentration
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2014-03-14
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Aripiprazole concentration in venous and capillary plasma
timeFrame: 14 time points over 3 days postdose
measure: Paliperidone concentration in venous and capillary plasma
timeFrame: 14 time points over 3 days postdose
measure: Olanzapine concentration in venous and capillary plasma
timeFrame: 14 time points over 3 days postdose
measure: Quetiapine concentration in venous and capillary plasma
timeFrame: 14 time points over 3 days postdose
measure: Risperidone concentration in venous and capillary plasma
timeFrame: 14 time points over 3 days postdose
Secondary outcomes:
measure: Number of participants with an adverse event as a measure of safety
timeFrame: Participants will be followed for the duration of hospital stay, an expected average of 3 days
Other outcomes:
Locations:
city: Garden Grove
country: United States
state: California
city: Kissimmee
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Hoffman Estates
country: United States
state: Illinois
city: Cedarhurst
country: United States
state: New York
city: Austin
country: United States
state: Texas
city: Banfield
country: Argentina
city: Ciudad Autónoma De Buenos Aires
country: Argentina
city: Cordoba
country: Argentina
city: La Plata
country: Argentina
city: Aalst
country: Belgium
city: Antwerpen
country: Belgium
city: Brussel
country: Belgium
city: Kortenberg
country: Belgium
city: Rio De Janeiro
country: Brazil
city: Valinhos
country: Brazil
city: Bourgas
country: Bulgaria
city: Berlin
country: Germany
city: Hamburg
country: Germany
city: Luebeck
country: Germany
city: Badajoz
country: Spain
city: Barcelona
country: Spain
city: Torrevieja
country: Spain
city: Zamora
country: Spain
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: