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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Paliperidone palmitate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paliperidone palmitate 50 mg<br>Paliperidone palmitate 50 milligram (mg) intramuscular (into the muscle) injection on Days 1, 8, 36 and 64. | Drug: Paliperidone palmitate<br>* 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.<br>* Other names: JNS010;|
| Experimental: Paliperidone palmitate 100 mg<br>Paliperidone palmitate 100 mg intramuscular injection on Days 1, 8, 36 and 64. | Drug: Paliperidone palmitate<br>* 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.<br>* Other names: JNS010;|
| Experimental: Paliperidone palmitate 150 mg<br>Paliperidone palmitate 150 mg intramuscular injection on Days 1, 8, 36 and 64. | Drug: Paliperidone palmitate<br>* 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.<br>* Other names: JNS010;|
| Experimental: Paliperidone palmitate 150/ 50 mg<br>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<br>* 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.<br>* Other names: JNS010;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Schizophrenia, Paliperidone Palmitate, JNS010