Schizophrenia
Conditions
Keywords
Schizophrenia, Risperidone, Risperdal, Paliperidone palmitate, Aripiprazole, Haloperidol, Olanzapine, Paliperidone, Perphenazine, Quetiapine
Brief summary
The study will assess the use of paliperidone palmitate compared with oral antipsychotic treatment in delaying time to a protocol-defined treatment failure over 15 months, in patients diagnosed with schizophrenia who have been incarcerated.
Detailed description
The primary objective of this study is to compare the efficacy of paliperidone palmitate with oral antipsychotic treatment in delaying time to a protocol-defined treatment failure over 15 months, in patients diagnosed with schizophrenia who have been incarcerated. Protocol-defined treatment failure is defined as arrest, psychiatric hospitalization, increase in psychiatric services to prevent imminent hospitalization, discontinuation of antipsychotic treatment due to inadequate efficacy, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to safety or tolerability or completed suicide. Protocol was amended on March 15, 2011 to reflect changes in the inclusion/exclusion criteria as well as the study objectives. Patients will receive either paliperidone palmitate 78, 117, 156, or 234 mg monthly by injection for fifteen months OR oral aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine, and risperidone at doses selected by the study doctor.
Interventions
DRUGpaliperidone
flexible dosing as prescribed by the study doctor for 15 months
DRUGrisperidone
flexible dosing as prescribed by the study doctor for 15 months
DRUGhaloperidole
flexible dosing as prescribed by the study doctor for 15 months
DRUGperphenazine
flexible dosing as prescribed by the study doctor for 15 months
DRUGaripiprazole
flexible dosing as prescribed by the study doctor for 15 months
DRUGquetiapine
flexible dosing as prescribed by the study doctor for 15 months
DRUGpaliperidone palmitate
78, 117, 156, or 234 mg monthly injection for 15 months
DRUGolanzapine
flexible dosing as prescribed by the study doctor for 15 months
Sponsors
Janssen Scientific Affairs, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Must be able to understand and sign the informed consent form approved by the Institutional Review Board (IRB) * Must successfully answer all the questions on the Informed Consent quiz indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study * Have a current diagnosis of schizophrenia * Taking no more than 1 oral antipsychotic on the day before randomization * Have been placed into custody at least twice with one of them leading to incarceration within the 24 months previous to study start, with the last release occurring within the 90 days before the first day of screening * in the opinion of the investigator, may benefit from a change in their prior antipsychotic treatment * Have available a designated individual (eg, family member, case manager, significant other, probation/parole officer) who has knowledge of the patient and is generally aware of the patient's daily activities, and who agrees to let the study site personnel know of changes in the patients circumstances when the patient is not able to provide this information, ie, arrests, protocol-defined hospitalizations, emergency room visits, becoming homeless, etc. * Have either an address or phone number where they can be reached, or be accessible to the designated individual * Must agree to receive regular injections for 15 months if randomly assigned to the paliperidone palmitate treatment group, or continue with oral study medication treatment for 15 months if randomly assigned to the oral antipsychotic treatment group * Women must be postmenopausal (for at least 2 years), surgically sterile (hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy), abstinent, or if sexually active, be practicing a highly effective method of birth control
Exclusion criteria
* Allergies, hypersensitivity (anaphylaxis-type reaction), or intolerance to risperidone or paliperidone * Actively abusing intravenous drugs within the past 3 months or have an opiate dependence disorder * Have a positive urine drug screen test for barbiturates, cocaine, amphetamines, or opiates at screening * Women who are pregnant or breast-feeding, or planning to become pregnant * Have received injectable antipsychotic treatment within 2 injection cycles prior to screening * Received treatment with clozapine within 3 months of screening * Are at a high risk of violence in the next 15 months, in the opinion of the investigator * who have a history of sex offenses including felony sex offenses, child molestation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Treatment Failure | From date of randomization up to Month 15 | Time to first treatment failure was the time from participant randomization to the first treatment failure, which was a composite endpoint consisting of any of the following events: arrest/incarceration, psychiatric hospitalization, discontinuation of antipsychotic treatment due to safety or tolerability, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to inadequate efficacy, increase in level of psychiatric services to prevent imminent psychiatric hospitalization, suicide. A Treatment Failure Event Monitoring Board (EMB), blinded to individual participant treatment assignment, determined the occurrence and date of the first treatment failure event. |
| Percentage of Participants in Each Event Category of First Treatment Failure | From date of randomization up to Month 15 | First treatment failure was a composite endpoint consisting of any of the following events: arrest/incarceration, psychiatric hospitalization, discontinuation (D/C) of antipsychotic treatment due to safety or tolerability, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to inadequate efficacy, increase in level of psychiatric services to prevent imminent psychiatric hospitalization, suicide. A Treatment Failure Event Monitoring Board (EMB), blinded to individual participant treatment assignment, determined the occurrence and date of the first treatment failure event. Percentage of participants who experienced treatment failure due to any event and for each specific category of event were assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Psychiatric Hospitalization or Arrest/Incarceration | From date of randomization up to Month 15 | A time to parameter looking only at 2 component events of treatment failure: arrest or incarceration, and psychiatric hospitalization. An arrest was defined as the taking of a participant into custody by legal authority, for any reason. Incarceration was defined as involuntary confinement by an officer of the law. Psychiatric hospitalization was an inpatient psychiatric hospitalization that occurred due to the participant's clinically significant worsening of symptoms of schizophrenia. |
| Change From Baseline in Personal and Social Performance (PSP) Total Score During Overall Treatment Duration | Baseline up to Month 15 | The PSP score assesses the degree of difficulty a participant exhibit over a 1 month period within 4 domains of behavior: a) socially useful activities, b) personal and social relationships, c) self-care, and d) disturbing and aggressive behavior. The investigators rate participants' degree of difficulty in each of the 4 domains using a 6-point Likert scale (from 0=absent to 5=very severe). The domain ratings were then transformed to PSP total score ranging from 1 to 100. Higher PSP total scores denote better functioning. A score between 71 and 100 represents normal to mild degree of dysfunction; a score between 31 and 70 represents varying degree of difficulty; and a score \<=30 represents poor function that requires intensive supervision. |
| Time to First Psychiatric Hospitalization | From date of randomization up to Month 15 | A time-to parameter looking only at 1 component event of treatment failure: psychiatric hospitalization. Time to first psychiatric hospitalization was admission date of the psychiatric hospitalization recorded in the Assessment of Treatment Failure - Psychiatric Hospitalization. |
| Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score During Overall Treatment Duration | Baseline up to Month 15 | The CGI-S rating scale was a 7-point global assessment of symptom severity with scores determined by clinician as follows: 1=Not ill, 2=Very Mild, 3= Mild, 4= Moderate, 5= Marked, 6= Severe, and 7= Extremely Severe. The higher the score the worse the illness. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paliperidone Palmitate Intramuscular injection, 234 milligram (mg) on Day 1, 156 mg on Day 8, followed by flexible monthly maintenance dosing as per investigator's discretion starting on Day 38 up to 15 months. | 226 |
| Oral Antipsychotics One of 7 oral antipsychotics (aripiprazole, haloperidol, olanzapine, paliperidone, perphenazine, quetiapine, and risperidone) that the investigator specified as appropriate for the participant was administered as per clinical practice for up to 15 months. | 218 |
| Total | 444 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 5 | 4 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 53 | 55 |
| Overall Study | Noncompliance with Study Drug | 0 | 3 |
| Overall Study | Other | 32 | 36 |
| Overall Study | Physician Decision | 5 | 4 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Randomized but not Treated | 4 | 2 |
| Overall Study | Withdrawal by Subject | 37 | 27 |
Baseline characteristics
| Characteristic | Total | Oral Antipsychotics | Paliperidone Palmitate |
|---|---|---|---|
| Age, Continuous | 38.1 years STANDARD_DEVIATION 10.47 | 38.6 years STANDARD_DEVIATION 10.36 | 37.7 years STANDARD_DEVIATION 10.57 |
| Baseline Clinical Global Impression - Severity (CGI-S) Total Score | 3.8 Units on a scale STANDARD_DEVIATION 0.75 | 3.9 Units on a scale STANDARD_DEVIATION 0.7 | 3.8 Units on a scale STANDARD_DEVIATION 0.8 |
| Baseline Personal and Social Performance (PSP) Total Score | 54.9 Units on a scale STANDARD_DEVIATION 12.76 | 55.0 Units on a scale STANDARD_DEVIATION 12.73 | 54.8 Units on a scale STANDARD_DEVIATION 12.83 |
| Sex: Female, Male Female | 61 Participants | 28 Participants | 33 Participants |
| Sex: Female, Male Male | 383 Participants | 190 Participants | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 178 / 226 | 155 / 218 |
| serious Total, serious adverse events | 42 / 226 | 53 / 218 |
Outcome results
Primary
Percentage of Participants in Each Event Category of First Treatment Failure
First treatment failure was a composite endpoint consisting of any of the following events: arrest/incarceration, psychiatric hospitalization, discontinuation (D/C) of antipsychotic treatment due to safety or tolerability, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to inadequate efficacy, increase in level of psychiatric services to prevent imminent psychiatric hospitalization, suicide. A Treatment Failure Event Monitoring Board (EMB), blinded to individual participant treatment assignment, determined the occurrence and date of the first treatment failure event. Percentage of participants who experienced treatment failure due to any event and for each specific category of event were assessed.
Time frame: From date of randomization up to Month 15
Population: eITT population included all ITT participants who had their study assessments for time period between randomization date and eITT end point. The eITT end point for paliperidone palmitate was the last injection date+28 days and for oral antipsychotics was the last prescription date + the number of days' supply + 1 day.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paliperidone Palmitate | Percentage of Participants in Each Event Category of First Treatment Failure | Treatment Failure Due to Any Event | 39.8 percentage of participants |
| Paliperidone Palmitate | Percentage of Participants in Each Event Category of First Treatment Failure | Arrest/incarceration | 21.2 percentage of participants |
| Paliperidone Palmitate | Percentage of Participants in Each Event Category of First Treatment Failure | Psychiatric hospitalization | 8.0 percentage of participants |
| Paliperidone Palmitate | Percentage of Participants in Each Event Category of First Treatment Failure | D/C due to safety/tolerability | 6.6 percentage of participants |
| Paliperidone Palmitate | Percentage of Participants in Each Event Category of First Treatment Failure | Treatment supplementation | 2.2 percentage of participants |
| Paliperidone Palmitate | Percentage of Participants in Each Event Category of First Treatment Failure | D/C due to inadequate efficacy | 0.4 percentage of participants |
| Paliperidone Palmitate | Percentage of Participants in Each Event Category of First Treatment Failure | Increase in level of psychiatric services | 1.3 percentage of participants |
| Paliperidone Palmitate | Percentage of Participants in Each Event Category of First Treatment Failure | Suicide | 0 percentage of participants |
| Oral Antipsychotics | Percentage of Participants in Each Event Category of First Treatment Failure | Suicide | 0 percentage of participants |
| Oral Antipsychotics | Percentage of Participants in Each Event Category of First Treatment Failure | Treatment Failure Due to Any Event | 53.7 percentage of participants |
| Oral Antipsychotics | Percentage of Participants in Each Event Category of First Treatment Failure | Treatment supplementation | 2.8 percentage of participants |
| Oral Antipsychotics | Percentage of Participants in Each Event Category of First Treatment Failure | Arrest/incarceration | 29.4 percentage of participants |
| Oral Antipsychotics | Percentage of Participants in Each Event Category of First Treatment Failure | Increase in level of psychiatric services | 1.8 percentage of participants |
| Oral Antipsychotics | Percentage of Participants in Each Event Category of First Treatment Failure | Psychiatric hospitalization | 11.9 percentage of participants |
| Oral Antipsychotics | Percentage of Participants in Each Event Category of First Treatment Failure | D/C due to inadequate efficacy | 4.1 percentage of participants |
| Oral Antipsychotics | Percentage of Participants in Each Event Category of First Treatment Failure | D/C due to safety/tolerability | 3.7 percentage of participants |
Primary
Time to First Treatment Failure
Time to first treatment failure was the time from participant randomization to the first treatment failure, which was a composite endpoint consisting of any of the following events: arrest/incarceration, psychiatric hospitalization, discontinuation of antipsychotic treatment due to safety or tolerability, treatment supplementation with another antipsychotic due to inadequate efficacy, discontinuation of antipsychotic treatment due to inadequate efficacy, increase in level of psychiatric services to prevent imminent psychiatric hospitalization, suicide. A Treatment Failure Event Monitoring Board (EMB), blinded to individual participant treatment assignment, determined the occurrence and date of the first treatment failure event.
Time frame: From date of randomization up to Month 15
Population: Explanatory Intent-to-Treat (eITT) population included all ITT participants who had their study assessments for time period between randomization date and eITT end point. The eITT end point for paliperidone palmitate was the last injection date+28 days and for oral antipsychotics was the last prescription date + the number of days' supply + 1 day.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paliperidone Palmitate | Time to First Treatment Failure | 416 Days |
| Oral Antipsychotics | Time to First Treatment Failure | 226 Days |
Secondary
Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score During Overall Treatment Duration
The CGI-S rating scale was a 7-point global assessment of symptom severity with scores determined by clinician as follows: 1=Not ill, 2=Very Mild, 3= Mild, 4= Moderate, 5= Marked, 6= Severe, and 7= Extremely Severe. The higher the score the worse the illness.
Time frame: Baseline up to Month 15
Population: eITT population. 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone Palmitate | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score During Overall Treatment Duration | -0.48 Units on a scale | Standard Error 0.038 |
| Oral Antipsychotics | Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score During Overall Treatment Duration | -0.43 Units on a scale | Standard Error 0.037 |
Secondary
Change From Baseline in Personal and Social Performance (PSP) Total Score During Overall Treatment Duration
The PSP score assesses the degree of difficulty a participant exhibit over a 1 month period within 4 domains of behavior: a) socially useful activities, b) personal and social relationships, c) self-care, and d) disturbing and aggressive behavior. The investigators rate participants' degree of difficulty in each of the 4 domains using a 6-point Likert scale (from 0=absent to 5=very severe). The domain ratings were then transformed to PSP total score ranging from 1 to 100. Higher PSP total scores denote better functioning. A score between 71 and 100 represents normal to mild degree of dysfunction; a score between 31 and 70 represents varying degree of difficulty; and a score \<=30 represents poor function that requires intensive supervision.
Time frame: Baseline up to Month 15
Population: eITT population. 'N' (number of participants analyzed) signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone Palmitate | Change From Baseline in Personal and Social Performance (PSP) Total Score During Overall Treatment Duration | 5.75 Units on a scale | Standard Error 0.69 |
| Oral Antipsychotics | Change From Baseline in Personal and Social Performance (PSP) Total Score During Overall Treatment Duration | 5.36 Units on a scale | Standard Error 0.69 |
Secondary
Time to First Psychiatric Hospitalization
A time-to parameter looking only at 1 component event of treatment failure: psychiatric hospitalization. Time to first psychiatric hospitalization was admission date of the psychiatric hospitalization recorded in the Assessment of Treatment Failure - Psychiatric Hospitalization.
Time frame: From date of randomization up to Month 15
Population: eITT population included all ITT participants who had their study assessments for time period between randomization date and eITT end point. The eITT end point for paliperidone palmitate was the last injection date+28 days and for oral antipsychotics was the last prescription date + the number of days' supply + 1 day.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paliperidone Palmitate | Time to First Psychiatric Hospitalization | NA Days |
| Oral Antipsychotics | Time to First Psychiatric Hospitalization | NA Days |
Secondary
Time to First Psychiatric Hospitalization or Arrest/Incarceration
A time to parameter looking only at 2 component events of treatment failure: arrest or incarceration, and psychiatric hospitalization. An arrest was defined as the taking of a participant into custody by legal authority, for any reason. Incarceration was defined as involuntary confinement by an officer of the law. Psychiatric hospitalization was an inpatient psychiatric hospitalization that occurred due to the participant's clinically significant worsening of symptoms of schizophrenia.
Time frame: From date of randomization up to Month 15
Population: eITT population included all ITT participants who had their study assessments for time period between randomization date and eITT end point. The eITT end point for paliperidone palmitate was the last injection date+28 days and for oral antipsychotics was the last prescription date + the number of days' supply + 1 day.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Paliperidone Palmitate | Time to First Psychiatric Hospitalization or Arrest/Incarceration | NA Days |
| Oral Antipsychotics | Time to First Psychiatric Hospitalization or Arrest/Incarceration | 274 Days |