Schizophrenia
Conditions
Keywords
Schizophrenia, Risperidone, Risperdal, Paliperidone Palmitate, Invega Sustenna
Brief summary
The study will assess the use of paliperidone palmitate compared with oral risperidone in delaying time to relapse in patients recently diagnosed with schizophrenia who are at high risk of relapse.
Detailed description
This is a Prospective, Randomized, Active-controlled, Rater-blinded Study to to assess the efficacy of paliperidone palmitate compared with oral risperidone in delaying time to relapse in patients recently diagnosed with schizophrenia who are at high risk of relapse. Recently diagnosed is defined as first diagnosis of any psychotic disorder within 5 years prior to screening. High risk of relapse is defined as having documented occurrence of 3 periods of breakthrough symptoms that required a change in patient care per the investigator's judgment (e.g., increase in dose, addition of a new drug, increase in the level of psychiatric care, notable increases in the frequency or intensity of patient contact required to maintain outpatient status, psychiatric hospitalization, etc.) within the previous 24 months, including 1 such period within the previous 6 months. Safety evaluations will include Adverse Event (AE) reporting, hematology and clinical chemistry laboratory tests, vital signs, electrocardiogram (ECG), and evaluations of suicidality and sexual functioning. Patients will receive either paliperidone palmitate 50, 75, 100, or 150 mg eq. monthly by injection for two years or oral risperidone 2, 4, 6, or 8 mg tabs once daily for two years.
Interventions
DRUGpaliperidone palmitate
50, 75, 100, or 150 mg eq. monthly injection for 2 years
DRUGoral risperidone
2, 4, 6, or 8 mg tabs once daily for two years
Sponsors
Ortho-McNeil Janssen Scientific Affairs, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
* Patients must be, in the opinion of the investigator, able to understand the informed consent form approved by the Institutional Review Board (IRB) or Independent Ethics Committee (IEC), as appropriate * All patients must sign the study informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study * Must have a current diagnosis of schizophrenia * must have had 3 periods of breakthrough symptoms that required a change in patient care as determined by the investigator (e.g. increase in dose, addition of a new drug, hospitalization, increase in the level of psychiatric care, notable increases in the frequency or intensity of patient contact required to maintain outpatient status, etc.) within the previous 24 months, including 1 such period within the previous 6 months * Women must be postmenopausal, surgically sterile, or otherwise be incapable of pregnancy, abstinent, or if sexually active, be practicing a highly effective method of birth control before entry, and must agree to continue to use the same method of contraception throughout the study * Women of childbearing potential must have a negative urine pregnancy test at screening * Patients must be cooperative and reliable, agree to receive regular injections, and be willing/able to adhere to the prohibitions and restrictions specified in this protocol.
Exclusion criteria
* Patients who are unable to provide their own consent or are involuntarily committed to psychiatric hospitalization * Have attempted suicide within 12 months before screening or are at imminent risk of suicide or violent behavior * Have a positive urine drug screen test for barbiturates, cocaine, amphetamines, or opiates at screening * Patients who are in their first episode of psychosis * Patients currently meeting criteria for any other Axis I diagnosis except substance abuse or an Axis II diagnosis of Mental Retardation or Borderline Personality Disorder * Meet the Diagnostic and Statistical Manual of Mental Health Disorders fourth edition (DSM-IV) definition of substance dependence (except for nicotine and caffeine dependence) within 6-months prior to entry * Patients with known allergies, hypersensitivity (anaphylaxis-type reaction), or intolerance to paliperidone palmitate, risperidone, Risperdal®, Risperdal® Consta®, or INVEGA® or its excipients * Patients who received Long Acting Therapy (LAT) treatment within 2 injection cycles prior to screening * Women who are pregnant or breast-feeding, or planning to become pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Relapse During Relapse Prevention Phase | 24 months | Time to relapse during the relapse prevention phase was the primary efficacy variable of the study. Each case of potential relapse event were to be reviewed in a blinded fasion by an independent Relapse Monitoring Board, comprised of experts in the diagnostic, clinical and therapeutic management of schizophrenia. |
Countries
Brazil, Bulgaria, Canada, China, Colombia, Czechia, India, Malaysia, Russia, South Korea, Ukraine, United States
Participant flow
Recruitment details
This trial was intended to recruit patients from multiple sites in North America, Europe, and Asia.
Pre-assignment details
Eligible patients were to be treated with paliperdione palmitate for up to 25 weeks (stabilization phase). Patients meeting stabilization criteria were to be randomized to either paliperidone palmitate or oral risperidone and be treated for 24 months (relapse prevention phase).
Participants by arm
| Arm | Count |
|---|---|
| Paliperidone Palmitate 50, 75, 100, or 150 mg equivalent (eq.) monthly injection | 162 |
| Total | 162 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Relapse Prevention Phase (24 Months) | Study Closed by Sponsor | 2 |
| Stabilization Phase (25 Weeks) | Adverse Event | 4 |
| Stabilization Phase (25 Weeks) | Failed to Meet Stability Criteria | 2 |
| Stabilization Phase (25 Weeks) | Lack of Efficacy | 3 |
| Stabilization Phase (25 Weeks) | Lost to Follow-up | 5 |
| Stabilization Phase (25 Weeks) | Patient Moved Away | 2 |
| Stabilization Phase (25 Weeks) | Prohibited Medication During Study | 1 |
| Stabilization Phase (25 Weeks) | Study Closed by Sponsor | 139 |
| Stabilization Phase (25 Weeks) | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Paliperidone Palmitate |
|---|---|
| Age at First Diagnosis of Schizophrenia | 24.1 years STANDARD_DEVIATION 4.61 |
| Age Continuous | 27 years STANDARD_DEVIATION 4.55 |
| Age, Customized 18-23 years | 46 participants |
| Age, Customized 24-29 years | 62 participants |
| Age, Customized 30-35 years | 54 participants |
| Clinical Global Impression of Severity (CGI-S) | 4.4 units on a scale STANDARD_DEVIATION 0.56 |
| Current Schizophrenia Diagnosis Disorganized (295.10) | 6 participants |
| Current Schizophrenia Diagnosis Paranoid (295.30) | 142 participants |
| Current Schizophrenia Diagnosis Residual (295.60) | 1 participants |
| Current Schizophrenia Diagnosis Undifferentiated (295.90) | 13 participants |
| Positive and Negative Syndrome Scale (PANSS) Total Score | 85.9 units on a scale STANDARD_DEVIATION 13.65 |
| Sex: Female, Male Female | 54 Participants |
| Sex: Female, Male Male | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 50 / 162 |
| serious Total, serious adverse events | 6 / 162 |
Outcome results
Primary
Time to Relapse During Relapse Prevention Phase
Time to relapse during the relapse prevention phase was the primary efficacy variable of the study. Each case of potential relapse event were to be reviewed in a blinded fasion by an independent Relapse Monitoring Board, comprised of experts in the diagnostic, clinical and therapeutic management of schizophrenia.
Time frame: 24 months
Population: The analysis population was to include all randomized patients who took at least one dose of study medication (ITT population). However, due to early study termination, only 2 patients were randomized and they did not have sufficient follow up. Hence the planned efficacy analysis could not be carried out.