Schizophrenia
Conditions
Keywords
Schizophrenia, Paliperidone, Paliperidone palmitate, Risperidone, Risperidone long acting injection, R092670
Brief summary
The purpose of this study is to compare the efficacy of paliperidone palmitate and risperidone long acting injection (LAI) in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) along with safety and tolerability.
Detailed description
This is a randomized (assigned by chance), open-label (all people know the identity of the intervention), active-controlled, parallel-group (a medical research study comparing the response in two or more groups of participants receiving different treatments), multicenter (when more than one hospital or medical school team work on a medical research study) comparative study in participants with schizophrenia. This study comprises a screening period of not more than 7 days and a 13-week open-label treatment period. Paliperidone palmitate will be administered as intramuscular injection (injection of a substance into a muscle) of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. at Day 8, flexible dose on Day 36 (50 or 100 mg eq.) and on Day 64 (50, 100 or 150 mg eq.) depending on investigator's discretion. Risperidone LAI will be administered at a dose of 25 mg at Day 8 and Day 22, flexible dose on Day 36 (25 or 37.5 mg) and Day 64 (25, 37.5, or 50 mg). Dose on Day 50 is the same as Day 36 and dose on Day 78 is the same as Day 64. Participants will receive oral risperidone tablets (1 to 6 mg/day) for the first 4 weeks of the open-label treatment period. Each participant may receive oral risperidone tablets (1 to 2 mg daily) for up to 3 weeks at Day 36 and Day 64 if the dose of risperidone LAI was increased on Day 36 and Day 64. Efficacy will primarily be assessed using the Positive and Negative Syndrome Scale (PANSS). Participants' safety will also be assessed.
Interventions
DRUGPaliperidone palmitate (R092670)
Paliperidone palmitate suspension for intramuscular injection at a dose of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. on Day 8, flexible dose, either 50 or 100 mg eq on Day 36 and 50, 100, or 150 mg eq.on Day 64 depending on investigator's discretion.
DRUGRisperidone
Risperidone LAI intramuscular at a dose of 25 mg on Day 8 and Day 22; flexible dose of either 25 or 37.5 mg on Day 36 with same dose on Day 50; and either 25, 37.5, or 50 mg on Day 64 with same dose on Day 78; along with oral risperidone 2 mg tablet on Day 1, flexible doses (1-6 mg/day) for first 28 days; and 1-2 mg/day during Day 36-57 and Day 64-85 if the dose of risperidone LAI was increased on Day 36 and Day 64.
Sponsors
Xian-Janssen Pharmaceutical Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants who meet diagnostic criteria for schizophrenia according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) (disorganized type \[295.10\], catatonic type \[295.20\], paranoid type \[295.30\], residual type \[295.60\], or undifferentiated type \[295.90\]) for at least 1 year before screening and prior medical records, written documentation, or verbal information obtained from previous psychiatric providers obtained by the investigator must be consistent with the diagnosis of schizophrenia * A total Positive and Negative Syndrome Scale (PANSS) score between 60 and 120, inclusive, at screening and baseline * Body mass index (BMI) of equal to or greater than 17.0 kilogram per meter square (kg/m\^2) * Female participants must be postmenopausal for at least 2 years, surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control before study entry and throughout the study * Be capable of self-administering study medication (applies to oral supplementation) or have assistance with study medication administration consistently available throughout the first 4 weeks of the study
Exclusion criteria
* A primary, active DSM-IV diagnosis on Axis I other than schizophrenia * A decrease of at least 25 percent in the total PANSS score between screening and baseline * Participants who have previously participated in this study * A DSM-IV diagnosis of active substance dependence within 3 months before screening (nicotine and caffeine are not exclusionary) * History of treatment resistance as defined by failure to respond to 2 adequate treatments with different antipsychotic medications (an adequate treatment is defined as a minimum of 6 weeks at maximum tolerated dosage)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 92 or Early Withdrawal | Baseline, Day 92 or early withdrawal | 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 rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 (absent) to 210 (extreme psychopathology). Higher change scores indicate worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Personal and Social Performance (PSP) Score at Day 92 or Early Withdrawal | Baseline, Day 92 or early withdrawal | This PSP assesses the degree of a participant's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (1, absent to 4, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Participants with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; \<= 30, functioning so poorly as to require intensive supervision. |
| Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Day 92 or Early Withdrawal | Baseline, Day 92 or early withdrawal | The CGI-S rating scale is a 7 point 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 change scores indicate worsening. |
| Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal | Baseline, Day 92 or early withdrawal | The self-administered sleep VAS scale (0-100 millimeter \[mm\]) rates quality of sleep (QoS) and daytime drowsiness (DD). Participants indicate mark on the scale to represent how well they have slept in the previous 7 days, score ranges from 0 mm (very badly) to 100 mm (very well); and how often they have felt drowsy within the previous 7 days, from 0 mm (not at all) to 100 mm (all the time). |
| Percentage of Participants Who Responded to PANSS Total Score at Day 92 or Early Withdrawal | Day 92 or early withdrawal | A responder is defined as a participant who improved from baseline in the PANSS total score by 30 percent or more. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paliperidone Palmitate Paliperidone palmitate suspension for intramuscular injection at a dose of 150 milligram equivalent (mg eq.) at baseline, 100 mg eq. on Day 8, flexible dose, either 50 or 100 mg eq on Day 36 and 50, 100, or 150 mg eq. on Day 64 depending on investigator's discretion. | 229 |
| Risperidone Long Acting Injection (LAI) Risperidone LAI intramuscular at a dose of 25 milligram (mg) on Day 8 and Day 22; flexible dose of either 25 or 37.5 mg on Day 36 with same dose on Day 50; and either 25, 37.5, or 50 mg on Day 64 with same dose on Day 78; along with oral risperidone 2 mg tablet on Day 1, flexible doses (1-6 mg/day) for first 28 days; and 1-2 mg/day during Day 36-57 and Day 64-85 if the dose of risperidone LAI was increased on Day 36 and Day 64. | 223 |
| Total | 452 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 5 |
| Overall Study | Lack of Efficacy | 22 | 9 |
| Overall Study | Lost to Follow-up | 9 | 14 |
| Overall Study | Other | 8 | 4 |
| Overall Study | Pregnancy | 2 | 0 |
| Overall Study | Protocol Violation | 3 | 1 |
| Overall Study | Withdrawal by Subject | 16 | 5 |
Baseline characteristics
| Characteristic | Paliperidone Palmitate | Total | Risperidone Long Acting Injection (LAI) |
|---|---|---|---|
| Age Categorical 18-25 Years | 87 Participants | 179 Participants | 92 Participants |
| Age Categorical <18 Years | 0 Participants | 0 Participants | 0 Participants |
| Age Categorical 26-50 Years | 125 Participants | 239 Participants | 114 Participants |
| Age Categorical 51-65 Years | 17 Participants | 34 Participants | 17 Participants |
| Age Categorical >65 Years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 32 years STANDARD_DEVIATION 10.75 | 31.7 years STANDARD_DEVIATION 10.88 | 31.5 years STANDARD_DEVIATION 11.03 |
| Sex: Female, Male Female | 142 Participants | 271 Participants | 129 Participants |
| Sex: Female, Male Male | 87 Participants | 181 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 115 / 229 | 127 / 223 |
| serious Total, serious adverse events | 3 / 229 | 8 / 223 |
Outcome results
Primary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 92 or Early Withdrawal
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 rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 (absent) to 210 (extreme psychopathology). Higher change scores indicate worsening.
Time frame: Baseline, Day 92 or early withdrawal
Population: Per Protocol Analysis Set included participants who received at least 2 injections of study medication had minimum 5 weeks of exposure to study treatment; had baseline and at least 1 post randomization measurement for primary efficacy variable and who did not have major protocol violations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Palmitate | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 92 or Early Withdrawal | Baseline | 82.1 Units on scale | Standard Deviation 11.95 |
| Paliperidone Palmitate | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 92 or Early Withdrawal | Change at Day 92 or Early Withdrawal | -23.6 Units on scale | Standard Deviation 16.28 |
| Risperidone Long Acting Injection (LAI) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 92 or Early Withdrawal | Baseline | 84.4 Units on scale | Standard Deviation 12.69 |
| Risperidone Long Acting Injection (LAI) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Day 92 or Early Withdrawal | Change at Day 92 or Early Withdrawal | -26.9 Units on scale | Standard Deviation 15.43 |
95% CI: [-5.2, 0.63]ANCOVA
Secondary
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Day 92 or Early Withdrawal
The CGI-S rating scale is a 7 point 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 change scores indicate worsening.
Time frame: Baseline, Day 92 or early withdrawal
Population: Per Protocol Analysis Set. Here N (Number of Participants Analyzed) represents number of participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Palmitate | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Day 92 or Early Withdrawal | Baseline | 4.9 Units on scale | Standard Deviation 0.82 |
| Paliperidone Palmitate | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Day 92 or Early Withdrawal | Change at Day 92 or Early Withdrawal | -1.5 Units on scale | Standard Deviation 1.24 |
| Risperidone Long Acting Injection (LAI) | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Day 92 or Early Withdrawal | Baseline | 5.0 Units on scale | Standard Deviation 0.81 |
| Risperidone Long Acting Injection (LAI) | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Day 92 or Early Withdrawal | Change at Day 92 or Early Withdrawal | -1.7 Units on scale | Standard Deviation 1.16 |
95% CI: [-0.33, 0.1]ANCOVA
Secondary
Change From Baseline in Personal and Social Performance (PSP) Score at Day 92 or Early Withdrawal
This PSP assesses the degree of a participant's dysfunction within 4 domains of behavior: socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behavior. The score ranges from 1 to 100, divided into 10 equal intervals to rate the degree of difficulty (1, absent to 4, very severe) in each of the 4 domains. Based on the four domains there will be one total score. Participants with a score of 71 to 100 have a mild degree of difficulty; from 31 to 70, varying degrees of disability; \<= 30, functioning so poorly as to require intensive supervision.
Time frame: Baseline, Day 92 or early withdrawal
Population: Per Protocol Analysis Set. Here N (Number of Participants Analyzed) represents number of participants who were evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Palmitate | Change From Baseline in Personal and Social Performance (PSP) Score at Day 92 or Early Withdrawal | Change at Day 92 or Early Withdrawal | 16.8 Units on scale | Standard Deviation 14.76 |
| Paliperidone Palmitate | Change From Baseline in Personal and Social Performance (PSP) Score at Day 92 or Early Withdrawal | Baseline | 47.8 Units on scale | Standard Deviation 12.42 |
| Risperidone Long Acting Injection (LAI) | Change From Baseline in Personal and Social Performance (PSP) Score at Day 92 or Early Withdrawal | Baseline | 45.3 Units on scale | Standard Deviation 11.29 |
| Risperidone Long Acting Injection (LAI) | Change From Baseline in Personal and Social Performance (PSP) Score at Day 92 or Early Withdrawal | Change at Day 92 or Early Withdrawal | 18.6 Units on scale | Standard Deviation 13.92 |
95% CI: [-2.14, 3.12]ANCOVA
Secondary
Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal
The self-administered sleep VAS scale (0-100 millimeter \[mm\]) rates quality of sleep (QoS) and daytime drowsiness (DD). Participants indicate mark on the scale to represent how well they have slept in the previous 7 days, score ranges from 0 mm (very badly) to 100 mm (very well); and how often they have felt drowsy within the previous 7 days, from 0 mm (not at all) to 100 mm (all the time).
Time frame: Baseline, Day 92 or early withdrawal
Population: Per Protocol Analysis Set.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Palmitate | Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal | QoS, Baseline | 64.1 millimeter (mm) | Standard Deviation 25.4 |
| Paliperidone Palmitate | Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal | QoS, Change at Day 92 or Early Withdrawal | 8.2 millimeter (mm) | Standard Deviation 26.95 |
| Paliperidone Palmitate | Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal | DD, Change at Day 92 or Early Withdrawal | -4.1 millimeter (mm) | Standard Deviation 27.26 |
| Paliperidone Palmitate | Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal | DD, Baseline | 29.9 millimeter (mm) | Standard Deviation 25.25 |
| Risperidone Long Acting Injection (LAI) | Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal | DD, Change at Day 92 or Early Withdrawal | -4.9 millimeter (mm) | Standard Deviation 24.12 |
| Risperidone Long Acting Injection (LAI) | Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal | QoS, Baseline | 66.6 millimeter (mm) | Standard Deviation 24.22 |
| Risperidone Long Acting Injection (LAI) | Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal | QoS, Change at Day 92 or Early Withdrawal | 10.0 millimeter (mm) | Standard Deviation 26.18 |
| Risperidone Long Acting Injection (LAI) | Change From Baseline in the Sleep Visual Analog Scale (VAS) Score at Day 92 or Early Withdrawal | DD, Baseline | 29.6 millimeter (mm) | Standard Deviation 23.5 |
Comparison: Statistical Analysis for Quality of sleep95% CI: [-0.67, 7.5]ANCOVA
Comparison: Statistical Analysis for Daytime drowsiness95% CI: [-5.04, 2.9]ANCOVA
Secondary
Percentage of Participants Who Responded to PANSS Total Score at Day 92 or Early Withdrawal
A responder is defined as a participant who improved from baseline in the PANSS total score by 30 percent or more.
Time frame: Day 92 or early withdrawal
Population: Per Protocol Analysis Set.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Paliperidone Palmitate | Percentage of Participants Who Responded to PANSS Total Score at Day 92 or Early Withdrawal | 70.7 Percentage of participants | 25.4 |
| Risperidone Long Acting Injection (LAI) | Percentage of Participants Who Responded to PANSS Total Score at Day 92 or Early Withdrawal | 78.4 Percentage of participants | 24.22 |
95% CI: [0.81, 1.01]Cochran-Mantel-Haenszel