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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT02087579

Collaborator

(none)

305

Enrollment

Locations

Arms

Duration (Months)

12.7

Patients Per Site

1.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Psychotic Disorders Schizophrenia Bipolar Disorder Depressive Disorder	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	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

305 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

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 Start Date :

Feb 1, 2014

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Dec 1, 2014

Arms and Interventions

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®

Outcome Measures

Primary Outcome Measures

Aripiprazole concentration in venous and capillary plasma [14 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 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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country
1	Garden Grove	California	United States
2	Kissimmee	Florida	United States
3	Atlanta	Georgia	United States
4	Hoffman Estates	Illinois	United States
5	Cedarhurst	New York	United States
6	Austin	Texas	United States
7	Banfield		Argentina
8	Ciudad Autónoma De Buenos Aires		Argentina
9	Cordoba		Argentina
10	La Plata		Argentina
11	Aalst		Belgium
12	Antwerpen		Belgium
13	Brussel		Belgium
14	Kortenberg		Belgium
15	Rio De Janeiro		Brazil
16	Valinhos		Brazil
17	Bourgas		Bulgaria
18	Berlin		Germany
19	Hamburg		Germany
20	Luebeck		Germany
21	Badajoz		Spain
22	Barcelona		Spain
23	Torrevieja		Spain
24	Zamora		Spain