A Clinical Pharmacology Study of JNS010 (Paliperidone Palmitate) in Patients With Schizophrenia

Clinical Pharmacology Study of JNS010 (Paliperidone Palmitate) in Subjects With Schizophrenia

The purpose of this study is to evaluate the pharmacokinetics (study of what the body does to a drug) and safety of paliperidone palmitate ranging from 75 to 150 milligram equivalents in repeated doses (4 injections) administered in the deltoid muscle (muscle in the shoulder) or gluteal muscle (group of muscles present in the buttocks) in participants with schizophrenia.

Study Overview

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

Detailed Description

This is a multicenter (study conducted at multiple sites), open label (all people know the identity of the intervention), randomized (the study medication is assigned by chance), parallel-group (each group of participants will be treated at the same time) study. Approximately, 60 participants will be enrolled in the study. This study will consist of a screening phase (maximum 14 days), an observation phase (92 days), and a follow-up phase (98 days). Participants will be randomly assigned to treatment group A, B, or C. During the observation phase, participants will receive injections of paliperidone palmitate of concentration ranging from 75 to 150 milligram equivalents in the deltoid muscle or gluteal muscle as applicable on Days 1, 8, 36, and 64 alternating between sides (left/right). Safety evaluations will include assessment of adverse events, clinical laboratory tests, electrocardiogram, vital signs, physical examination, injection site reaction, drug-induced extrapyramidal symptoms scale, and visual analog scale which will be evaluated throughout the study. The total study duration for each participant will be approximately 190 days.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Phase 1

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 had to have the capability to provide informed consent in writing to participate in the study

• Participants with a diagnosis of schizophrenia in accordance with the diagnostic criteria for Diagnostic and Statistical Manual of Mental Disorders -IV-TR (DSM-IV-TR)
• Participants whose psychiatric symptom is considered stable by the investigator/subinvestigator at the time of giving informed consent
• Participants with a Positive and Negative Syndrome Scale (PANSS) score of less than or equal to 4 (moderate) in the following 9 items at screening: delusion, conceptual disorganization, hallucinatory behavior, excitement, grandiosity, suspiciousness/persecution, hostility, uncooperativeness, poor impulse control
• Participants with an experience of taking a risperidone formulation or a paliperidone formulation by 8 days before the initial day (Day 1) of the study treatment

Exclusion Criteria:- DSM-IV-TR diagnosis other than schizophrenia

• DSM-IV-TR diagnosis of substance-related disorders within 180 days before the date of screening
• At a risk of suicide or other-injurious behavior as considered by the investigator/subinvestigator , and participants with a history of suicide attempts
• Concurrent condition of Parkinson's disease (except for drug-induced extrapyramidal syndrome) - Concurrent condition or history of symptomatic cerebrovascular accident

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A; Participants will receive 4 injections of paliperidone palmitate 150 milligram in the deltoid muscle on Days 1, 8, 36, and 64.	Drug: Paliperidone palmitate; Participants will receive 4 injections of paliperidone palmitate of concentration ranging from 75 to 150 milligram equivalents in deltoid or gluteal muscle as randomized to treatment group A, B, or C on Days 1, 8, 36, and 64.; Other Names: JNS010
Experimental: Treatment B; Participants will receive 4 injections of paliperidone palmitate 75 milligram in the deltoid muscle on Days 1, 8, 36, and 64.	Drug: Paliperidone palmitate; Participants will receive 4 injections of paliperidone palmitate of concentration ranging from 75 to 150 milligram equivalents in deltoid or gluteal muscle as randomized to treatment group A, B, or C on Days 1, 8, 36, and 64.; Other Names: JNS010
Experimental: Treatment C; Participants will receive 4 injections of paliperidone palmitate 75 milligram in the gluteal muscle on Days 1, 8, 36, and 64.	Drug: Paliperidone palmitate; Participants will receive 4 injections of paliperidone palmitate of concentration ranging from 75 to 150 milligram equivalents in deltoid or gluteal muscle as randomized to treatment group A, B, or C on Days 1, 8, 36, and 64.; Other Names: JNS010

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of unchanged drug (Paliperidone palmitate)		Days 1 to 190
Plasma concentration of active metabolite (paliperidone)		Days 1 to 190
Plasma concentration of enantiomer of paliperidone palmitate (R078543)		Days 1 to 190
Plasma concentration of enantiomer paliperidone palmitate (R078544)		Days 1 to 190
Maximum Observed Plasma Concentration (Cmax) of paliperidone palmitate	The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration.	Days 1 to 190
Time to Reach Maximum Observed Plasma Concentration (Tmax) of paliperidone palmitate	The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.	Days 1 to 190
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of paliperidone palmitate	The Area Under the Curve From Time Zero to End of Dosing Interval (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 to 190
Number of participants with adverse events		Up to Day 190

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Positive and Negative Syndrome Scale for Schizophrenia (PANSS)	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). Higher scores indicate worsening.	Screening, Baseline (Day 1), Days 8, 36, 64, and 92
Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Score	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 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.	Screening, Baseline (Day 1), Days 8, 36, 64, and 92

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Publications and helpful links

Helpful Links

• Clinical pharmacology study of JNS010 (Paliperidone palmitate) in patients with schizophrenia

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: September 10, 2013
• First Submitted That Met QC Criteria: September 10, 2013
• First Posted (Estimate): September 16, 2013

Study Record Updates

• Last Update Posted (Estimate): September 16, 2013
• Last Update Submitted That Met QC Criteria: September 10, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Schizophrenia; Clinical Pharmacology; 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: CR100413; PALM-JPN-3 (Other Identifier: Janssen Pharmaceutical K.K., Japan)