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

Phase 1
Completed
Conditions
Schizophrenia
Interventions
Registration Number
NCT01942382
Lead Sponsor
Janssen Pharmaceutical K.K.
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
76
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Treatment APaliperidone palmitateParticipants will receive 4 injections of paliperidone palmitate 150 milligram in the deltoid muscle on Days 1, 8, 36, and 64.
Treatment BPaliperidone palmitateParticipants will receive 4 injections of paliperidone palmitate 75 milligram in the deltoid muscle on Days 1, 8, 36, and 64.
Treatment CPaliperidone palmitateParticipants will receive 4 injections of paliperidone palmitate 75 milligram in the gluteal muscle on Days 1, 8, 36, and 64.
Primary Outcome Measures
NameTimeMethod
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
Time to Reach Maximum Observed Plasma Concentration (Tmax) of paliperidone palmitateDays 1 to 190

The Tmax is defined as actual sampling time to reach maximum observed analyte concentration.

Maximum Observed Plasma Concentration (Cmax) of paliperidone palmitateDays 1 to 190

The Plasma Concentration (Cmax) is defined as maximum observed analyte concentration.

Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of paliperidone palmitateDays 1 to 190

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.

Number of participants with adverse eventsUp to Day 190
Secondary Outcome Measures
NameTimeMethod
Change from baseline in Positive and Negative Syndrome Scale for Schizophrenia (PANSS)Screening, Baseline (Day 1), Days 8, 36, 64, and 92

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.

Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale ScoreScreening, Baseline (Day 1), Days 8, 36, 64, and 92

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.

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