Schizophrenia
Conditions
Keywords
Schizophrenia, R092670, Paliperidone Palmitate, Paliperidone palmitate 3 month formulation (PP3M)
Brief summary
The purpose of this study is to evaluate the efficacy of paliperidone palmitate 3 month formulation (PP3M) compared with placebo in delay of the time to first occurrence of relapse of the symptoms of schizophrenia.
Detailed description
This is a randomized (the study drug is assigned by chance), double blind (neither physician nor patient knows the treatment that the patient receives), parallel group (each group of patients will be treated at the same time), placebo-controlled (an inactive substance is compared with a drug to test whether the drug has a real effect in a clinical trial) multicenter study. The study consists of 4 phases: a Screening Phase (up to 3 weeks); a 17-week flexible dose open-label Transition Phase (open-label phase means that all people know the identity of the intervention); a 12-week fixed dose open-label Maintenance Phase; and a randomized, double-blind, fixed dose, placebo-controlled relapse prevention phase (referred to as the Double-blind Phase). Patients who meet specific stabilization criteria will enter the Double-blind Phase at Week 29. Patients will be randomly assigned, in a 1:1 ratio, to receive either a fixed dose of PP3M or placebo. The Double-blind Phase will be of variable duration; patients will remain in the study until they experience a relapse event or meet discontinuation criteria.
Interventions
DRUGPP3M 175 mg eq.
Type= exact number, unit= mg eq., number= 175, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.
DRUGPP3M 263 mg eq.
Type= exact number, unit= mg eq., number= 263, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.
DRUGPP3M 350 mg eq.
Type= exact number, unit= mg eq., number= 350, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.
DRUGPP3M 525 mg eq.
Type= exact number, unit= mg eq., number= 525, form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.
DRUGPlacebo (20% Intralipid emulsion)
Form= injection, route= intramuscular use. One injection every three months up to the patient has a relapse event or meet discontinuation criteria.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients with schizophrenia for more than 1 year * A total score in the Positive and Negative Syndrome Scale (PANSS) \< 120 * Signed informed consent * Women must not be pregnant, breastfeeding, and if capable of pregnancy must practice an effective method of birth control * Men must agree to use a double-barrier method of birth control * Be medically stable on the basis of clinical laboratory tests, physical examination, medical history, vital signs, and electrocardiogram (ECG)
Exclusion criteria
* A diagnosis other than schizophrenia, e.g., dissociative disorder, bipolar disorder, major depressive disorder, schizoaffective disorder, schizophreniform disorder, autistic disorder, primary substance-induced psychotic disorder, dementia-related psychosis * Relevant history or current presence of any significant or unstable medical condition(s) determined to be clinically significant by the Investigator (ie, obesity, diabetes, heart disease etc) * A diagnosis of substance dependence within 6 months before screening * History of neuroleptic malignant syndrome (NMS) or tardive dyskinesia * Clozapine use in the last 2 months when used for treatment-resistant or treatment-refractory illness * Clinically significant findings in biochemistry, hematology, ECG or urinalysis results * Any other disease or condition that, in the opinion of the investigator, would make participation not in the best interest of the patient or that could prevent, limit, or confound the protocol-specified assessments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Relapse During the Double-Blind Phase | Approximately Week 60 | Time to relapse defined as the time between participant randomization into the double blind Phase and the first documentation of a relapse event. Median time to relapse was estimated by the Kaplan-Meier method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Positive and Negative Syndrome Scale (PANSS) (Total Score) From Baseline to Endpoint in the Double-Blind Phase | Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60) | The PANSS provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items). Each item is rated 1 (absent) to 7 (extreme). The total score ranging from 30 to 210. Higher scores indicate more severe neuropsychiatric symptoms of schizophrenia. |
| Change in Clinical Global Impression Severity (CGI-S) Scale From Baseline to Endpoint in the Double-Blind Phase | Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60) | The CGI-S rating scale is used to rate the severity of a participant's overall clinical condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe). |
| Change in Personal and Social Performance (PSP) Scale From Baseline to Endpoint in the Double-Blind Phase | Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60) | The PSP scale measures personal and social functioning in the domains of: a) Socially useful activities, b) Personal and social relationships, c) Self-care, and d) Disturbing and aggressive behavior. The results of the assessment were converted to a numerical score which ranges from 1 to 100. A score lying between 71 and 100 indicates a mild degree of dysfunction; scores between 31 and 70 indicate varying degrees of difficulty, and a participant with a score of \<=30 had functioning so poor that he or she required intensive supervision. |
Countries
Colombia, Malaysia, Mexico, Romania, South Korea, Turkey (Türkiye), Ukraine, United States
Participant flow
Pre-assignment details
A total of 509 participants were enrolled in to the study and 506 participants were entered the Open-label Transition and received at least one dose of study drug (PP1M). 2 participants were enrolled but not received study drug and 1 participant was screen failure.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Phase: Placebo Matching placebo \[20 percent (%) Intralipid solution\] was administered intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. | 145 |
| Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M) Paliperidone palmitate was administered at a dose of 175, 263, 350, or 525 milligram equivalents (mg eq) intramuscular (IM) injection every 12 weeks up to participants had a relapse event or met discontinuation criteria. Participants received the same dose of study agent that was administered on Day 120 of the Maintenance Phase. | 160 |
| Total | 305 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| DOUBLE BLIND PHASE | Adverse Event | 0 | 0 | 1 | 0 |
| DOUBLE BLIND PHASE | Lost to Follow-up | 0 | 0 | 1 | 3 |
| DOUBLE BLIND PHASE | Other | 0 | 0 | 9 | 2 |
| DOUBLE BLIND PHASE | Pregnancy | 0 | 0 | 1 | 0 |
| DOUBLE BLIND PHASE | Protocol Violation | 0 | 0 | 1 | 0 |
| DOUBLE BLIND PHASE | Withdrawal by Subject | 0 | 0 | 10 | 7 |
| MAINTENANCE PHASE | Adverse Event | 0 | 10 | 0 | 0 |
| MAINTENANCE PHASE | Failed Randomization Criteria | 0 | 13 | 0 | 0 |
| MAINTENANCE PHASE | Lack of Efficacy | 0 | 9 | 0 | 0 |
| MAINTENANCE PHASE | Lost to Follow-up | 0 | 5 | 0 | 0 |
| MAINTENANCE PHASE | Other | 0 | 10 | 0 | 0 |
| MAINTENANCE PHASE | Protocol Violation | 0 | 12 | 0 | 0 |
| MAINTENANCE PHASE | Withdrawal by Subject | 0 | 15 | 0 | 0 |
| TRANSITION PHASE | Adverse Event | 16 | 0 | 0 | 0 |
| TRANSITION PHASE | Death | 1 | 0 | 0 | 0 |
| TRANSITION PHASE | Failed Maintenance Phase Criteria | 8 | 0 | 0 | 0 |
| TRANSITION PHASE | Lack of Efficacy | 19 | 0 | 0 | 0 |
| TRANSITION PHASE | Lost to Follow-up | 19 | 0 | 0 | 0 |
| TRANSITION PHASE | Other | 9 | 0 | 0 | 0 |
| TRANSITION PHASE | Protocol Violation | 4 | 0 | 0 | 0 |
| TRANSITION PHASE | Withdrawal by Subject | 51 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Double-Blind Phase: Placebo | Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M) | Total |
|---|---|---|---|
| Age, Continuous | 38.5 years STANDARD_DEVIATION 11.16 | 37.1 years STANDARD_DEVIATION 10.87 | 37.8 years STANDARD_DEVIATION 11.01 |
| Region of Enrollment Colombia | 12 participants | 13 participants | 25 participants |
| Region of Enrollment Malaysia | 11 participants | 12 participants | 23 participants |
| Region of Enrollment Mexico | 10 participants | 8 participants | 18 participants |
| Region of Enrollment Romania | 14 participants | 13 participants | 27 participants |
| Region of Enrollment South Korea | 4 participants | 2 participants | 6 participants |
| Region of Enrollment Turkey | 5 participants | 6 participants | 11 participants |
| Region of Enrollment Ukraine | 63 participants | 74 participants | 137 participants |
| Region of Enrollment United States | 26 participants | 32 participants | 58 participants |
| Sex: Female, Male Female | 35 Participants | 42 Participants | 77 Participants |
| Sex: Female, Male Male | 110 Participants | 118 Participants | 228 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 317 / 506 | 77 / 145 | 98 / 160 |
| serious Total, serious adverse events | 33 / 506 | 15 / 145 | 4 / 160 |
Outcome results
Primary
Time to Relapse During the Double-Blind Phase
Time to relapse defined as the time between participant randomization into the double blind Phase and the first documentation of a relapse event. Median time to relapse was estimated by the Kaplan-Meier method.
Time frame: Approximately Week 60
Population: The intent-to-treat (ITT) double blind (DB) population included all participants who were randomly assigned to treatment during the Double-blind Phase and received at least one dose of Double-blind study agent.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double-Blind Phase: Placebo | Time to Relapse During the Double-Blind Phase | 395.0 Days |
| Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M) | Time to Relapse During the Double-Blind Phase | NA Days |
Secondary
Change in Clinical Global Impression Severity (CGI-S) Scale From Baseline to Endpoint in the Double-Blind Phase
The CGI-S rating scale is used to rate the severity of a participant's overall clinical condition on a 7-point scale ranging from 1 (not ill) to 7 (extremely severe).
Time frame: Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60)
Population: Intent-to-treat (ITT) double blind (DB) population included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study agent. Missing data was imputed using LOCF method. Here N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Phase: Placebo | Change in Clinical Global Impression Severity (CGI-S) Scale From Baseline to Endpoint in the Double-Blind Phase | Baseline | 2.8 Units on a Scale | Standard Deviation 0.65 |
| Double-Blind Phase: Placebo | Change in Clinical Global Impression Severity (CGI-S) Scale From Baseline to Endpoint in the Double-Blind Phase | Change at Endpoint (Approximately Week 60) | 0.4 Units on a Scale | Standard Deviation 0.87 |
| Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M) | Change in Clinical Global Impression Severity (CGI-S) Scale From Baseline to Endpoint in the Double-Blind Phase | Baseline | 2.7 Units on a Scale | Standard Deviation 0.68 |
| Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M) | Change in Clinical Global Impression Severity (CGI-S) Scale From Baseline to Endpoint in the Double-Blind Phase | Change at Endpoint (Approximately Week 60) | 0.1 Units on a Scale | Standard Deviation 0.6 |
Secondary
Change in Personal and Social Performance (PSP) Scale From Baseline to Endpoint in the Double-Blind Phase
The PSP scale measures personal and social functioning in the domains of: a) Socially useful activities, b) Personal and social relationships, c) Self-care, and d) Disturbing and aggressive behavior. The results of the assessment were converted to a numerical score which ranges from 1 to 100. A score lying between 71 and 100 indicates a mild degree of dysfunction; scores between 31 and 70 indicate varying degrees of difficulty, and a participant with a score of \<=30 had functioning so poor that he or she required intensive supervision.
Time frame: Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60)
Population: Intent-to-treat (ITT) double blind (DB) population included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study agent. Missing data was imputed using LOCF method. Here N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Phase: Placebo | Change in Personal and Social Performance (PSP) Scale From Baseline to Endpoint in the Double-Blind Phase | Baseline | 68.5 Units on a Scale | Standard Deviation 8.93 |
| Double-Blind Phase: Placebo | Change in Personal and Social Performance (PSP) Scale From Baseline to Endpoint in the Double-Blind Phase | Change at Endpoint (Approximately Week 60) | -4.2 Units on a Scale | Standard Deviation 9.7 |
| Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M) | Change in Personal and Social Performance (PSP) Scale From Baseline to Endpoint in the Double-Blind Phase | Baseline | 68.9 Units on a Scale | Standard Deviation 9.34 |
| Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M) | Change in Personal and Social Performance (PSP) Scale From Baseline to Endpoint in the Double-Blind Phase | Change at Endpoint (Approximately Week 60) | -0.5 Units on a Scale | Standard Deviation 6.63 |
Secondary
Change in Positive and Negative Syndrome Scale (PANSS) (Total Score) From Baseline to Endpoint in the Double-Blind Phase
The PANSS provides a total score (sum of the scores of all 30 items) and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items). Each item is rated 1 (absent) to 7 (extreme). The total score ranging from 30 to 210. Higher scores indicate more severe neuropsychiatric symptoms of schizophrenia.
Time frame: Baseline (Day 1 prior to randomization) and Endpoint (Approximately Week 60)
Population: Intent-to-treat (ITT) double blind (DB) population included all participants who were randomly assigned to treatment during DB Phase and received at least 1 dose of DB study agent. Missing data was imputed using LOCF method. Here N (Number of Participants Analyzed) signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Phase: Placebo | Change in Positive and Negative Syndrome Scale (PANSS) (Total Score) From Baseline to Endpoint in the Double-Blind Phase | Baseline | 54.3 Units on a Scale | Standard Deviation 9.2 |
| Double-Blind Phase: Placebo | Change in Positive and Negative Syndrome Scale (PANSS) (Total Score) From Baseline to Endpoint in the Double-Blind Phase | Change at Endpoint (Approximately Week 60) | 6.7 Units on a Scale | Standard Deviation 14.4 |
| Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M) | Change in Positive and Negative Syndrome Scale (PANSS) (Total Score) From Baseline to Endpoint in the Double-Blind Phase | Baseline | 54.8 Units on a Scale | Standard Deviation 9.96 |
| Double-Blind Phase: Paliperidone Palmitate 3-Month (PP3M) | Change in Positive and Negative Syndrome Scale (PANSS) (Total Score) From Baseline to Endpoint in the Double-Blind Phase | Change at Endpoint (Approximately Week 60) | -0.5 Units on a Scale | Standard Deviation 8.36 |