A Pharmacokinetic and Safety Study of Paliperidone Palmitate (JNS010) in Participants With Schizophrenia

A Repeated Dose Study of JNS010 (Paliperidone Palmitate) in Patients With Schizophrenia

The purpose of this study is to assess the pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time) and safety of paliperidone palmitate in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self).

Study Overview

• Status: Completed
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Paliperidone palmitate

Detailed Description

This is a multicenter (when more than one hospital or medical school team work on a medical research study), open-label (all people know the identity of the intervention), randomized (the study drug is assigned by chance), parallel-group (Each group of participants will be treated at the same time), comparison study to assess the pharmacokinetics and safety of paliperidone palmitate (study medication) in participants with schizophrenia. The study comprises a 64-day Treatment period and a 155-day Follow-up period. The participants will be randomly assigned to one of the four study groups. The study medication will be administered on Days 1, 8, 36 and 64. Pharmacokinetics of the study medication will be assessed as primary outcome. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Ichikawa, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Participants who have been diagnosed with schizophrenia in accordance with the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)
• Participants may be inpatients or outpatients
• Participants who have been taking an oral antipsychotic medication for at least 28 days before the date of informed consent
• Participants with a Positive and Negative Syndrome Scale (PANSS) score of less than or equal to 4 (moderate) at screening
• Participants who have taken risperidone by the start of investigational treatment and the record can be confirmed Exclusion Criteria
• Participants who have been diagnosed with a mental disease other than schizophrenia in accordance with the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV)
• Participants who have been diagnosed with substance-related disorders (except nicotine and caffeine dependence)
• Participants with complicated parkinson's disease (a progressive disorder of the central nervous system, seen usually in older persons, in which there is muscle weakness, trembling and sweating)
• Participants with a complication of or with a history of convulsive disease such as epilepsy (seizure disorder)
• Participants with a complication of or with a history of cerebro-vascular accident (stroke), neuroleptic malignant syndrome (high fever, rigid muscles, shaking, confusion, sweating more than usual, increased heart rate or blood pressure, or muscle pain or weakness) or physical exhaustion associated with the state of dehydration (lose of water and minerals in the body) or malnutrition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Paliperidone palmitate 50 mg; Paliperidone palmitate 50 milligram (mg) intramuscular (into the muscle) injection on Days 1, 8, 36 and 64.	Drug: Paliperidone palmitate; Paliperidone palmitate aqueous suspension for injection 0.5, 1.0, 1.5 milliliter equivalent to 50, 100, 150 mg paliperidone respectively as intramuscular injection on Days 1, 8, 36 and 64.; Other Names: JNS010
EXPERIMENTAL: Paliperidone palmitate 100 mg; Paliperidone palmitate 100 mg intramuscular injection on Days 1, 8, 36 and 64.	Drug: Paliperidone palmitate; Paliperidone palmitate aqueous suspension for injection 0.5, 1.0, 1.5 milliliter equivalent to 50, 100, 150 mg paliperidone respectively as intramuscular injection on Days 1, 8, 36 and 64.; Other Names: JNS010
EXPERIMENTAL: Paliperidone palmitate 150 mg; Paliperidone palmitate 150 mg intramuscular injection on Days 1, 8, 36 and 64.	Drug: Paliperidone palmitate; Paliperidone palmitate aqueous suspension for injection 0.5, 1.0, 1.5 milliliter equivalent to 50, 100, 150 mg paliperidone respectively as intramuscular injection on Days 1, 8, 36 and 64.; Other Names: JNS010
EXPERIMENTAL: Paliperidone palmitate 150/ 50 mg; Paliperidone palmitate 150 mg intramuscular injection on Day 1 and paliperidone palmitate 50 mg intramuscular injection on Days 8, 36 and 64.	Drug: Paliperidone palmitate; Paliperidone palmitate aqueous suspension for injection 0.5, 1.0, 1.5 milliliter equivalent to 50, 100, 150 mg paliperidone respectively as intramuscular injection on Days 1, 8, 36 and 64.; Other Names: JNS010

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 8	The pre-dose plasma concentration (Cpredose) at Day 8 is defined as the plasma concentration obtained before a dose is given on Day 8. The mean Cpredose at Day 8 was measured in nanogram per milliliter (ng/ml).	Day 8
Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 36	The Cpredose at Day 36 is defined as the plasma concentration obtained before a dose is given on Day 36. The mean Cpredose at Day 36 was measured in ng/ml.	Day 36
Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 64	The Cpredose at Day 64 is defined as the plasma paliperidone concentration obtained before a dose is given on Day 64. The mean Cpredose at Day 64 was measured in ng/ml.	Day 64
Paliperidone Pre-dose Plasma Concentration (Cpredose) at Day 92	The Cpredose at Day 92 is defined as the plasma paliperidone concentration obtained after the treatment interval of the study drug (that is 4 weeks) passed after the final dose (Day 92). The mean Cpredose at Day 92 was measured in ng/ml.	Day 92
Maximum Observed Plasma Concentration (Cmax) of Paliperidone	The Cmax is defined as maximum observed analyte concentration.	Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Paliperidone	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)	The AUCtau is a measure of the plasma paliperidone concentration from time zero to end of dosing interval. It is used to characterize drug absorption.	Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal
Plasma Paliperidone Concentration at Steady State (Css av)	The Css av is defined as value of average analyte concentration at steady-state (after 4 Intramuscular Injections of Paliperidone Palmitate).	Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal
Paliperidone Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	Days 1, 8, 15, 22, 36, 50, 64, 67, 71, 74, 78, 85, 92, 106, 120, 134, 162, 190, 218 and early withdrawal
Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 8	The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).	Day 8
Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 22	The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).	Day 22
Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 50	The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).	Day 50
Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 78	The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).	Day 78
Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 92	The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).	Day 92
Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 120	The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).	Day 120
Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 162	The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).	Day 162
Number of Participants With Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Score at Day 218	The DIEPSS is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the average of the 8 item scores, for a total range of 0 (normal) to 4 (severe). Overall severity was assessed at 5 levels (0 [none, normal]; 1 [Very Mild]; 2 [Mild]; 3 [Moderate]; 4 [severe]).	Day 218

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive and Negative Syndrome Scale (PANSS) Total Score	The PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill).	Baseline, Day 8, 22, 50, 78 and 92
Number of Participants With Clinical Global Impression Severity (CGI-S) Score	The CGI-S rating scale is a 7 point (1-absent, 2-minimal, 3-mild, 4-moderate, 5-moderate severe, 6-severe, 7-extreme) global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. 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 participants". Higher scores indicate worsening.	Baseline, Day 8, 22, 50, 78 and 92

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (ACTUAL): April 1, 2008
• Study Completion (ACTUAL): April 1, 2008

Study Registration Dates

• First Submitted: May 15, 2012
• First Submitted That Met QC Criteria: May 23, 2012
• First Posted (ESTIMATE): May 25, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): June 5, 2013
• Last Update Submitted That Met QC Criteria: May 28, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Schizophrenia; Paliperidone Palmitate; JNS010
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Paliperidone Palmitate
• Other Study ID Numbers: CR013612; PALM-JPN-2 (OTHER: Janssen Pharmaceutical K.K., Japan)