A Study to Assess the Pharmacokinetics, Safety, and Tolerability of Paliperidone Palmitate in Patients With Schizophrenia

September 15, 2017 updated by: Janssen Research & Development, LLC

A Single-Dose, Open-Label, Randomized, Parallel-Group Study to Assess the Pharmacokinetics, Safety, and Tolerability of a Paliperidone Palmitate 3-Month Formulation in Subjects With Schizophrenia

The purpose of this study is to assess the pharmacokinetics, safety, and tolerability of a paliperidone palmitate 3-month formulation in patients with schizophrenia.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a multicenter, randomized (the study drug is assigned by chance), open-label (all people know the identity of the intervention), parallel-group (each group of patients will be initiated simultaneously) study in 4 panels (A, B, C and D). Each panel will comprise 2 single-dose treatment periods. In Period 1, all patients from the 4 panels will receive an intramuscular (i.m.) injection with 1 mg paliperidone as an immediate release (IR) solution to assess tolerability and allergic or hypersensitivity reactions potentially related to paliperidone, and to establish the relative bioavailability (the extent to which a drug or other substance becomes available to the body) of paliperidone palmitate versus paliperidone IR. Patients in Panels A and C will receive an i.m. injection with 1 mg paliperidone IR solution in the gluteal muscle, and patients in Panel B and D will receive an i.m. injection with 1 mg paliperidone IR solution in the deltoid or gluteal muscle. Patients who tolerate this injection and have completed all assessments on Day 5 of Period 1 will be enrolled in Period 2. In Period 2, patients will receive a single dose of 3-month paliperidone palmitate i.m. injection at the dosages defined for each panel. The study drug injection will be followed by a 96-hour observation period in Period 1, and a 364-day or 544-day observation period in Period 2. Successive study drug administrations will be separated by a washout period (period when receiving no treatment) of at least 7 and no more than 21 days. The total study length for all patients is from 53 weeks to a maximum of 58 weeks. Patients in Panel B, if consented, and Panel D will participate in the extension period of approximately 26 weeks in order to obtain additional assessments to be able to characterize the pharmacokinetics (PK) profile. Pharmacokinetics explores how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time. Therefore, for those who participate in the extension period, the total study duration will be approximately 84 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
328

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Aalst, Belgium
      • Diest, Belgium
  • Bulgaria
      • Bourgas N/A, Bulgaria
  • Croatia
      • Zagreb, Croatia
  • Israel
      • Beer Yaakov, Israel
      • Hod-Hasharon, Israel
      • Ramat Gan, Israel
  • Korea, Republic of
      • Incheon, Korea, Republic of
      • Jeonju-Si, Korea, Republic of
      • Seoul, Korea, Republic of
  • Malaysia
      • Johor Bahru, Malaysia
      • Kuala Lumpur, Malaysia
      • Perak, Malaysia
  • Slovakia
      • Bratislava, Slovakia
      • Michalovce, Slovakia
      • Rimavska Sobota, Slovakia
  • South Africa
      • Bloemfontein, South Africa
      • Cape Town, South Africa
  • Spain
      • Badajoz, Spain
      • Badalona, Spain
      • Barcelona, Spain
      • Sevilla, Spain
      • Zamora, Spain
  • Taiwan
      • Hua Lian, Taiwan
      • Taipei, Taiwan
      • Taoyuan, Taiwan
  • United States
    • Arkansas
      • Little Rock, Arkansas, United States
    • California
      • Cerritos, California, United States
      • Garden Grove, California, United States
      • Glendale, California, United States
      • National City, California, United States
      • Paramount, California, United States
    • Georgia
      • Atlanta, Georgia, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
    • Texas
      • Austin, Texas, United States
      • DeSoto, Texas, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients diagnosed with schizophrenia or schizoaffective disorder, for at least 1 year before screening
  • Clinically stable with no hospitalizations for schizophrenia exacerbation or change in current antipsychotic medications for 3 months prior to screening
  • Stabilized on antipsychotic medications other than risperidone, paliperidone, ziprasidone, clozapine, thioridazine, or any long acting injectable.
  • For panel D only, no detectable plasma concentration of risperidone or paliperidone > 0.1ng/mL at screening. A quantifiable and stable level of paliperidone not exceeding 0.25 ng/mL is allowed if such paliperidone value is explained by (documented) use of paliperidone palmitate (last dose administered > 12 months prior to baseline)
  • Has a total PANSS score of 70 or less at both screening and Day-1 (Period 1)
  • Woman is postmenopausal, surgically sterile, abstinent or, if sexually active, practices an effective method of birth control during participation in the study or for at least 6 months after the last dose of study drug, whichever is longer
  • Woman has negative pregnancy test at screening and on Day -1 of Period 1
  • Man agrees to use an adequate contraception method as deemed appropriate by the investigator and agrees to not donate sperm during participation in the study or for at least 6 months after the last dose of study drug, whichever is longer
  • Body Mass Index (BMI) between 17 and 35 kg/m2 (inclusive). Body weight of at least 50 kg for patients enrolled in panel A, B and C. For patients enrolled in panel D only: body weight of at least 47 kg

Exclusion Criteria:

  • Attempted suicide within 12 months before screening or is at imminent risk of suicide or violent behavior
  • Has diagnosis of alcohol or substance dependence, with the exception of nicotine or caffeine dependence, within 12 months prior to screening, or diagnosis of substance abuse within 3 months prior to screening
  • Has a positive drug screen test for barbiturates, cocaine, amphetamines or opiates, or has a positive alcohol screen test unless positive toxicology screen is explained by a prescribed allowed medication
  • Is in his/her first episode of psychosis
  • Has a history of or has a current clinically significant medical illness that the investigator considers should exclude the patients or that could interfere with the interpretation of the study results
  • Has clinically significant abnormal values at screening or at baseline for hematology, clinical chemistry or for urinalysis, as deemed appropriate by the investigator
  • Has a clinically relevant abnormality in the physical examination, vital signs or 12 lead electrocardiogram (ECG) at screening or at baseline as deemed appropriate by the investigator
  • Has a history or presence of circumstances that may increase the risk of the occurrence of torsade de pointes and/or sudden death in association with the use of drugs that prolong the QTc interval
  • Concomitant use of medications that the investigator considers should exclude the patients or that could interfere with the interpretation of the study results
  • Any other condition or circumstance that the investigator considers should exclude the patients or that could interfere with the interpretation of the study results

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Panel A
Panel A consists of 2 treatment groups
Drug: Paliperidone IR (Period 1)
Type= exact number, unit= mg, number=1, form= injection, route= intramuscular use. Single injection with 1 mg paliperidone IR in the gluteal or deltoid muscle.
Drug: Paliperidone palmitate F015 (Panel A: treatment group 1)
Type= exact number, unit= mg, number=300, form= injection, route= intramuscular use. Single injection with 300 mg eq. 3-month formulation paliperidone palmitate F015 manufactured by milling technique A, in the gluteal muscle.
Drug: Paliperidone palmitate F015 (Panel A: treatment group 2)
Type= exact number, unit= mg, number=300, form= injection, route= intramuscular use. Single injection with 300 mg eq. 3-month formulation paliperidone palmitate F015 manufactured by milling technique B, in the gluteal muscle.
Experimental: Panel B
Panel B consists of 5 treatment groups
Drug: Paliperidone IR (Period 1)
Type= exact number, unit= mg, number=1, form= injection, route= intramuscular use. Single injection with 1 mg paliperidone IR in the gluteal or deltoid muscle.
Drug: Paliperidone palmitate F015 (Panel B: treatment group 1)
Type= exact number, unit= mg, number= 75, form= injection, route= intramuscular use. Single injection with 75 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.
Drug: Paliperidone palmitate F015 (Panel B: treatment group 2)
Type= exact number, unit= mg, number=150, form= injection, route= intramuscular use. Single injection with 150 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.
Drug: Paliperidone palmitate F015 (Panel B: treatment group 3)
Type= exact number, unit= mg, number=450, form= injection, route= intramuscular use. Single injection with 450 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.
Drug: Paliperidone palmitate F015 (Panel B: treatment group 4)
Type= exact number, unit= mg, number=300, form= injection, route= intramuscular use. Single injection with 300 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.
Drug: Paliperidone palmitate F015 (Panel B: treatment group 5)
Type= exact number, unit= mg, number=450, form= injection, route= intramuscular use. Single injection with 450 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.
Experimental: Panel C
Panel C consists of 1 treatment group
Drug: Paliperidone IR (Period 1)
Type= exact number, unit= mg, number=1, form= injection, route= intramuscular use. Single injection with 1 mg paliperidone IR in the gluteal or deltoid muscle.
Drug: Paliperidone palmitate F016
Type= exact number, unit= mg, number=150, form= injection, route= intramuscular use. Single injection with 150 mg eq. 3-month formulation paliperidone palmitate F016 in the gluteal muscle.
Experimental: Panel D
Panel D consists of 4 treatment groups
Drug: Paliperidone IR (Period 1)
Type= exact number, unit= mg, number=1, form= injection, route= intramuscular use. Single injection with 1 mg paliperidone IR in the gluteal or deltoid muscle.
Drug: Paliperidone palmitate F015 (Panel D: treatment group 1)
Type= exact number, unit= mg, number=525, form= injection, route= intramuscular use. Single injection with 525 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.
Drug: Paliperidone palmitate F015 (Panel D: treatment group 2)
Type= exact number, unit= mg, number=525, form= injection, route= intramuscular use. Single injection with 525 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.
Drug: Paliperidone palmitate F015 (Panel D: treatment group 3)
Type= exact number, unit= mg, number=350, form= injection, route= intramuscular use. Single injection with 350 mg eq. 3-month formulation paliperidone palmitate F015 in the gluteal muscle.
Drug: Paliperidone palmitate F015 (Panel D: treatment group 4)
Type= exact number, unit= mg, number=175, form= injection, route= intramuscular use. Single injection with 175 mg eq. 3-month formulation paliperidone palmitate F015 in the deltoid muscle.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Plasma concentration of Paliperidone (Period 1)
Time Frame: 14 time points over 96 hours
14 time points over 96 hours
Plasma concentration of Paliperidone (Period 2)
Time Frame: 29 time points over 544 days
29 time points over 544 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
The change from baseline in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) (Period 1)
Time Frame: Baseline and 96 hours
The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.
Baseline and 96 hours
Changes in Positive and Negative Syndrome Scale for Schizophrenia (PANSS) observed across multiple time points between baseline and 544 days (Period 2)
Time Frame: Baseline and 544 days
The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate worsening.
Baseline and 544 days
The change from baseline in Clinical Global Impression (CGI-S) (Period 1)
Time Frame: Baseline and 96 hours
The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a subject. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill subjects". Higher scores indicate worsening.
Baseline and 96 hours
Changes in Clinical Global Impression (CGI-S) observed across multiple time points between baseline and 544 days (Period 2)
Time Frame: Baseline and 544 days
The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a subject. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill subjects". Higher scores indicate worsening.
Baseline and 544 days
Changes from Baseline in Abnormal Involuntary Movement Scale (AIMS) for the ratings of dyskinesia (Period 1)
Time Frame: Baseline and 96 hours
The AIMS consists of 12 items to measure involuntary movements known as dyskinesia, with scores ranging from 0 (none) to 4 (severe).
Baseline and 96 hours
Changes in Abnormal Involuntary Movement Scale (AIMS) for the ratings of dyskinesia observed across multiple time points between baseline and 544 days (Period 2)
Time Frame: Baseline and 544 days
The AIMS consists of 12 items to measure involuntary movements known as dyskinesia, with scores ranging from 0 (none) to 4 (severe).
Baseline and 544 days
Changes from Baseline in Barnes Akathisia Rating Scale (BARS) for the ratings of akathisia (Period 1)
Time Frame: Baseline and 96 hours
The BARS is a scale to assess the presence and severity of drug-induced akathisia (inner restlessness). It is scored as follows: Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness are rated on a 4-point scale from 0 (normal or absence of restlessness) to 3 (intense restlessness). The Global Clinical Assessment of Akathisia uses a 6-point scale ranging from 0 (absent) to 5 (severe akathisia).
Baseline and 96 hours
Changes in Barnes Akathisia Rating Scale (BARS) for the ratings of akathisia observed across multiple time points between baseline and 544 days (Period 2)
Time Frame: Baseline and 544 days
The BARS is a scale to assess the presence and severity of drug-induced akathisia (inner restlessness). It is scored as follows: Objective Akathisia, Subjective Awareness of Restlessness and Subjective Distress Related to Restlessness are rated on a 4-point scale from 0 (normal or absence of restlessness) to 3 (intense restlessness). The Global Clinical Assessment of Akathisia uses a 6-point scale ranging from 0 (absent) to 5 (severe akathisia).
Baseline and 544 days
Changes from Baseline in Simpson and Angus Rating Scale (SAS) for the ratings of general extrapyramidal symptoms (EPS) (Period 1)
Time Frame: Baseline and 96 hours
The SAS is a 10-item instrument used to evaluate the presence and severity of extrapyramidal symptoms (EPS), such as akinesia (inability to initiate movement) and akathisia. Items are rated for severity on a 0 (normal) to 4 (severe symptoms) scale.
Baseline and 96 hours
Changes in Simpson and Angus Rating Scale (SAS) for the ratings of general extrapyramidal symptoms (EPS) observed across multiple time points between baseline and 544 days (Period 2)
Time Frame: Baseline and 544 days
The SAS is a 10-item instrument used to evaluate the presence and severity of extrapyramidal symptoms (EPS), such as akinesia (inability to initiate movement) and akathisia. Items are rated for severity on a 0 (normal) to 4 (severe symptoms) scale.
Baseline and 544 days
Changes from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) (Period 1)
Time Frame: Baseline and 96 hours
The Columbia-Suicide Severity Rating Scale (C-SSRS) rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent."
Baseline and 96 hours
Changes in Columbia-Suicide Severity Rating Scale (C-SSRS) observed across multiple time points between baseline and 544 days (Period 2)
Time Frame: Baseline and 544 days
The Columbia-Suicide Severity Rating Scale (C-SSRS) rates an individual's degree of suicidal ideation on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent."
Baseline and 544 days
Evaluation of the Injection Site (Period 1)
Time Frame: 96 hours
The investigator will evaluate the site of injection for redness, swelling, and induration. The evaluation will be assessed as 0 = absent, 1 = mild, 2 = moderate, 3 = severe.
96 hours
Evaluation of the Injection Site (Period 2)
Time Frame: Baseline through day 112
The investigator will evaluate the site of injection for redness, swelling, and induration. The evaluation will be assessed as 0 = absent, 1 = mild, 2 = moderate, 3 = severe.
Baseline through day 112
Incidence of Adverse Events as a Measure of Safety and Tolerability
Time Frame: Approximately 84 weeks
Approximately 84 weeks
Number of patients with abnormal clinical laboratory tests
Time Frame: Approximately 84 weeks
Approximately 84 weeks
Number of patients with abnormal findings in electrocardiogram, vital signs and physical examination
Time Frame: Approximately 84 weeks
Approximately 84 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Janssen Research & Development, LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 21, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 9, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 24, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 13, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 21, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 18, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 15, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CR012652
  • R092670PSY1005 (Other Identifier: Janssen Research & Development, LLC)
  • 2007-003581-17 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

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