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

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

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.

Study Overview

• Status: Completed
• Conditions: Depressive Disorder; Psychotic Disorders; Schizophrenia; Bipolar Disorder
• Intervention / Treatment: Drug: Aripiprazole, oral formulation; Drug: Olanzapine, oral formulation; Drug: Paliperidone, oral formulation; Drug: Paliperidone, LAI; Drug: Quetiapine, oral formulation; Drug: Risperidone, oral formulation; Drug: Risperidone, LAI

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.

• Study Type: Interventional
• Enrollment (Actual): 305
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Banfield, Argentina
  • Ciudad Autónoma De Buenos Aires, Argentina
  • Cordoba, Argentina
  • La Plata, Argentina
• Belgium
  • Aalst, Belgium
  • Antwerpen, Belgium
  • Brussel, Belgium
  • Kortenberg, Belgium
• Brazil
  • Rio De Janeiro, Brazil
  • Valinhos, Brazil
• Bulgaria
  • Bourgas, Bulgaria
• Germany
  • Berlin, Germany
  • Hamburg, Germany
  • Luebeck, Germany
• Spain
  • Badajoz, Spain
  • Barcelona, Spain
  • Torrevieja, Spain
  • Zamora, Spain
• United States
  • California
    • Garden Grove, California, United States
  • Florida
    • Kissimmee, Florida, United States
  • Georgia
    • Atlanta, Georgia, United States
  • Illinois
    • Hoffman Estates, Illinois, United States
  • New York
    • Cedarhurst, New York, United States
  • Texas
    • Austin, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Aripiprazole; Administration of oral formulation will continue at a participant's usual dose and dosing schedule.	Drug: Aripiprazole, oral formulation; Aripiprazole tablets will be administered orally (by mouth), at no dose restriction, as per the locally approved label indications.
Experimental: Cohort B: Olanzapine; Administration of oral formulation will continue at a participant's usual dose and dosing schedule.	Drug: Olanzapine, oral formulation; Olanzapine tablets will be administered orally, at no dose restriction as per the locally approved label indications.
Experimental: Cohort C: Paliperidone; Administration of prolonged-release (extended-release) tablets or long-acting injectables (LAI) will continue at a participant's usual dose and dosing schedule.	Drug: 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.; Other Names: INVEGA®; Drug: Paliperidone, LAI; Paliperidone long-acting injectable (LAI) i.e., paliperidone palmitate injections, will be administered per the locally approved label indications.; Other Names: INVEGA®
Experimental: Cohort D: Quetiapine; Administration of oral formulation will continue at a participant's usual dose and dosing schedule.	Drug: 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.
Experimental: Cohort E: Risperidone; Administration of oral formulation or LAI will continue at a participant's usual dose and dosing schedule.	Drug: Risperidone, oral formulation; Risperidone tablets will be administered orally, at no dose restriction, as per the locally approved label indications.; Other Names: RISPERDAL®; Drug: Risperidone, LAI; Risperidone LAI injections will be administered will be administered per the locally approved label indications.; Other Names: RISPERDAL®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Paliperidone concentration in venous and capillary plasma		14 time points over 3 days postdose
Olanzapine concentration in venous and capillary plasma		14 time points over 3 days postdose
Quetiapine concentration in venous and capillary plasma		14 time points over 3 days postdose
Risperidone concentration in venous and capillary plasma		14 time points over 3 days postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: February 17, 2014
• First Submitted That Met QC Criteria: March 13, 2014
• First Posted (Estimate): March 14, 2014

Study Record Updates

• Last Update Posted (Estimate): October 29, 2015
• Last Update Submitted That Met QC Criteria: October 28, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Schizophrenia; Bipolar Disorder; Depressive Disorder; Aripiprazole; Risperidone; Paliperidone; Psychotic Disorders; Quetiapine; Antipsychotics; Olanzapine; Capillary Concentration
• Additional Relevant MeSH Terms: Behavioral Symptoms; Pathologic Processes; Mood Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Bipolar and Related Disorders; Depression; Depressive Disorder; Schizophrenia; Disease; Psychotic Disorders; Mental Disorders; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Olanzapine; Aripiprazole; Paliperidone Palmitate; Quetiapine Fumarate; Risperidone
• Other Study ID Numbers: CR103695; 2013-005289-20 (EudraCT Number); INDIGOAPS1003 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No