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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Psychotic Disorders; Schizophrenia; Bipolar Disorder; Depressive Disorder

Treatments: Drug: Aripiprazole, oral formulation; Drug: Paliperidone, LAI; Drug: Risperidone, oral formulation; Drug: Paliperidone, oral formulation; Drug: Quetiapine, oral formulation; Drug: Risperidone, LAI; Drug: Olanzapine, oral formulation

Study type: Interventional

Funder types: Industry

Identifiers

NCT02087579

INDIGOAPS1003 (Other Identifier)

CR103695

2013-005289-20 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 305 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No 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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

305 participants in 5 patient groups

Cohort A: Aripiprazole

Experimental group

Description:

Administration of oral formulation will continue at a participant's usual dose and dosing schedule.

Treatment:

Drug: Aripiprazole, oral formulation

Cohort B: Olanzapine

Experimental group

Description:

Administration of oral formulation will continue at a participant's usual dose and dosing schedule.

Treatment:

Drug: Olanzapine, oral formulation

Cohort C: Paliperidone

Experimental group

Description:

Administration of prolonged-release (extended-release) tablets or long-acting injectables (LAI) will continue at a participant's usual dose and dosing schedule.

Treatment:

Drug: Paliperidone, oral formulation

Drug: Paliperidone, LAI

Cohort D: Quetiapine

Experimental group

Description:

Administration of oral formulation will continue at a participant's usual dose and dosing schedule.

Treatment:

Drug: Quetiapine, oral formulation

Cohort E: Risperidone

Experimental group

Description:

Administration of oral formulation or LAI will continue at a participant's usual dose and dosing schedule.

Treatment:

Drug: Risperidone, LAI

Drug: Risperidone, oral formulation