A Study of Paliperidone Palmitate 6-Month Formulation

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to assess the long-term safety and tolerability of paliperidone 6-month PP6M (Dose 1 or Dose 2 [milligram] mg eq.) and to provide access to PP6M in participants with schizophrenia completing the R092670PSY3015 study without relapse.

Official Title
-----------------
Single-arm, Open-label Extension to a Double-blind, Randomized, Active-controlled, Parallel-group Study of Paliperidone Palmitate 6-Month Formulation

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Drug: PP6M injection Dose 1
* Drug: PP6M injection Dose 2


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Completed the Double-blind Phase of Study R092670PSY3015 without relapse and continue to be willing to be treated with paliperidone palmitate 6 month injection (PP6M) Must, in the opinion of the investigator, be able to continue treatment at the same dose level (moderate or higher dose) as used during the Double-blind Phase of Study R092670PSY3015 at the time of screening for this study A woman of childbearing potential: a) Must have a negative pregnancy test on Day 1; b) Use contraception consistent with local regulations. A man must agree that during the study and for a minimum 12 months after receiving the last dose of the study intervention: a) His female partner(s) will use highly effective method pf contraception Sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study; and must be able to provide his or her own consent (that is, consent cannot be provided by a legal representative of the participant) In the opinion of the investigator, the patient would be able to participate for the duration of this study Exclusion Criteria: Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments Completed R092670PSY3015 while presenting adverse events deemed clinically relevant by the investigator, and which may interfere with safety and well-being of the participant If a man, has plans to father a child while enrolled in this study or within 12 months after the last dose of study intervention. Must not, if a woman, have plans to become pregnant while enrolled in this study or within 12 months after the last dose of study intervention

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paliperidone Palmitate 6 month(PP6M)<br>Participants who enter the this open-label extension study immediately after completing Double-blind Phase Study R092670PSY3015 (previous study) will receive Paliperidone Palmitate 6 month (PP6M) intramuscular (IM) injections, dose will be selected based on the unblinded dose level (moderate or higher) that the participant received during previous study. Participants in the moderate dose level will receive PP6M Dose 1 and higher dose level will receive PP6M Dose 2 during the open-label extension. The PP6M dose level may be adjusted (to Dose 1 or Dose 2) for every 6 month at Visits 3, 5, and 7, based on clinical judgment. Participants who enter this open-label extension study later (up to 3 months after they complete previous study) and were on a moderate or higher dose of PP3M (350 or 525 mg eq.) or PP1M (100 or 150 mg eq.) will receive initial dose of PP6M IM injection (Dose 1 or Dose 2) for every 6 months. | Drug: PP6M injection Dose 1<br>* Participants will receive Dose 1 PP6M intramuscular (IM) injection at Visit 1 (Day) then once every 6 month up to 24 months.<br>* Other names: R092670;Drug: PP6M injection Dose 2<br>* Participants will receive Dose 2 PP6M IM injection at Visit 1 (Day) then once every 6 month up to 24 months.<br>* Other names: R092670;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Relapse | Number of participants with relapse were reported. Relapse is defined as one or more of the following: a) Psychiatric hospitalization for schizophrenia (involuntary or voluntary admission to a psychiatric hospital for decompensation of the participant's schizophrenic symptoms); b) Emergency Department/Room/Ward visit due to a worsening of the participant's symptoms of schizophrenia, but a psychiatric hospitalization does not occur; c) The participant inflicts deliberate self-injury or exhibits violent behaviour resulting in suicide, clinically significant injury to him/herself or another person, or significant property damage; d) The participant has suicidal or homicidal ideation and aggressive behaviour that is clinically significant (in frequency and severity) in the investigator's judgment. | Up to Day 730 | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs are those events if they started after administration of the first dose and until 183 days after the last dose of study medication. | Up to Day 730 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale Score | Change from baseline in CGI-S scale score was reported. CGI-S is defined as clinician-rated scale that assesses the severity of mental illness on a scale of 0 to 7. Considering total clinical experience, a participant was assessed on severity of mental illness at the time of rating according to:1: normal, not at all ill; 2: borderline mentally ill; 3: mildly ill; 4: moderately ill; 5: markedly ill; 6: severely ill; 7: among the most extremely ill participants. A higher score implies a more severe condition. | Baseline up to Day 730 | 
| Change From Baseline in Personal and Social Performance (PSP) Scale Score | Change from baseline in PSP scale score was reported. The PSP scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Each domain was assessed on a 6-point scale, from 1 (absent) to 6 (very severe) (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe). PSP total score was calculated as sum of all the domain scores and ranges from 1 to 100. Participants with score of 71 to 100 had mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision. Higher score indicates better performance. | Baseline up to Day 730 | 
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score | Change from baseline in PANSS total score were reported. The neuropsychiatric symptoms of schizophrenia were assessed using the 30-item PANSS scale, which provides a total score (sum of the scores for all 30 items) and scores for 3 subscales: the 7-item positive-symptom (P) subscale, the 7-item negative-symptom (N) subscale, and the 16-item general-psychopathology symptom (G) subscale. Each item is rated on a scale of 1 (absent) to 7 (extreme). The PANSS total score ranges from 30 (absent disease)-210 (more severe neuropsychiatric symptoms of schizophrenia). | Baseline up to Day 730 |