Schizophrenia
Conditions
Keywords
Schizophrenia, JNS007ER, Positive and Negative Syndrome Scale (PANSS), Paliperidone, Extended Release Osmotic Controlled-Release Oral Delivery System (OROS) paliperidone
Brief summary
The purpose of this study is to evaluate the effectiveness and safety of Extended Release Osmotic Controlled-Release Oral Delivery System (OROS) Paliperidone compared to placebo in patients with Schizophrenia. Olanzapine will be used as a reference drug in the study.
Detailed description
This is a multicenter, double blind (neither the patient nor the physician knows whether drug or placebo is being taken, or at what dosage), randomized (patients are assigned different treatments based on chance), placebo- and active-controlled, parallel-group study. Patients will be randomized into 1 of 3 treatment groups to receive oral dosages of Extended Release (ER) Osmotic Controlled-Release Oral Delivery System (OROS) paliperidone 6 mg, olanzapine 10 mg, or placebo. They will receive two capsules of Paliperidone ER 3 mg, placebo or Olanzapine 5 mg once daily after breakfast for 6 weeks. The study will include a screening period, followed by double-blind treatment for 6 weeks.
Interventions
Type= exact number, unit= mg, number= 3, form= tablet, route= oral use. Two tablets once daily for 6 weeks.
DRUGPlacebo
Form= tablet, route= oral use. Two tablets once daily for 6 weeks.
DRUGOlanzapine
Type= exact number, unit= mg, number= 2.5, form= tablet, route= oral use. Four tablets once daily for 6 weeks.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have given their own consent in writing to participate in the study * Patients diagnosed with schizophrenia according to the diagnostic criteria of DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 295.30, 295.10, 295.20, 295.90, 295.60) * Patients who have acute symptoms of schizophrenia * Both inpatients and outpatients are acceptable
Exclusion criteria
* A DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) of a mental disease diagnosis other than schizophrenia * A DSM-IV diagnosis of substance-related disorder (except nicotine dependence and caffeine dependence) within 180 days before the screening test * Total PANSS (Positive and Negative Syndrome System) score at the screening test \<70 or \>120 * Patients treated with three or more types of antipsychotic within 28 days before the screening test * Parkinson's disease (except for those with drug-induced extra pyramidal symptoms) * Patients with a complication of or a past history of cerebrovascular accident * Patients with a complication of or a past history of diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Total Positive and Negative Syndrome Scale (PANSS). | Baseline and 6 weeks | PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Positive Subscale Score | Baseline and 6 weeks | The PANSS Positive Subscale assesses seven positive-symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology). |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Negative Subscale Score | Baseline and 6 weeks | The PANSS Negative Subscale assesses seven negative-symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology). |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - General Psychopathology Subscale Score | Baseline and 6 weeks | The PANSS General Psychopathology Subscale Score assesses 16 general psychopathology symptoms. The symptoms are rated on a 7-point scale, with a range of 16 (absent) to 112 (extreme psychopathology). |
| Proportion of Responders (≥30% Decrease in Total Positive and Negative Syndrome Scale [PANSS]) | Baseline and 6 weeks | Responders are subjects with 30% or more reduction from baseline in total PANSS score. PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill). |
| Change From Baseline in Clinical Global Impression Scale (CGI-S) | Baseline and 6 weeks | The CGI-S rating scale is a 7-point global assessment with scores as follows: 1 - Not ill, 2 - Very Mild, 3 - Mild, 4 - Moderate, 5 - Marked, 6 - Severe, and 7 - Extremely Severe. |
Countries
Japan
Participant flow
Pre-assignment details
Informed Consent was obtained from 394 patients. The actual number of patients randomized in the study was 321. 2 subjects discontinued before treatment. 319 subjects were treated and analyzed for safety. 318 subjects were analyzed for baseline characteristics and efficacy.
Participants by arm
| Arm | Count |
|---|---|
| Paliperidone Extended Release (ER) (JNS007ER) Two paliperidone ER (JNS007ER) 3 mg tablets once daily for 6 weeks | 134 |
| Placebo Two placebo tablets once daily for 6 weeks | 138 |
| Olanzapine Four olanzapine 2.5 mg tablets once daily for 6 weeks | 46 |
| Total | 318 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 13 | 3 |
| Overall Study | Lack of Efficacy | 32 | 64 | 11 |
| Overall Study | Physician Decision | 3 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 8 | 13 | 1 |
Baseline characteristics
| Characteristic | Paliperidone Extended Release (ER) (JNS007ER) | Placebo | Olanzapine | Total |
|---|---|---|---|---|
| Age, Continuous | 44.0 years STANDARD_DEVIATION 14.7 | 46.2 years STANDARD_DEVIATION 15.1 | 46.2 years STANDARD_DEVIATION 13.2 | 45.3 years STANDARD_DEVIATION 14.6 |
| Sex: Female, Male Female | 64 Participants | 66 Participants | 27 Participants | 157 Participants |
| Sex: Female, Male Male | 70 Participants | 72 Participants | 19 Participants | 161 Participants |
| Total Positive and Negative Syndrome Scale (PANSS) score | 92.0 scores on a scale STANDARD_DEVIATION 12.9 | 91.0 scores on a scale STANDARD_DEVIATION 11.2 | 94.1 scores on a scale STANDARD_DEVIATION 12.6 | 91.9 scores on a scale STANDARD_DEVIATION 12.2 |
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 | 109 / 134 | 110 / 138 | 40 / 47 |
| serious Total, serious adverse events | 4 / 134 | 1 / 138 | 2 / 47 |
Outcome results
Primary
Change From Baseline in the Total Positive and Negative Syndrome Scale (PANSS).
PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill).
Time frame: Baseline and 6 weeks
Population: Full Analysis Set excludes subjects who didn't receive test drug or didn't have post-treatment efficacy data. The Olanzapine (OLZ) group was set as an active drug group to examine clinical position of paliperidone (PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone Extended Release (ER) (JNS007ER) | Change From Baseline in the Total Positive and Negative Syndrome Scale (PANSS). | -9.1 scores on a scale | Standard Deviation 18.39 |
| Placebo | Change From Baseline in the Total Positive and Negative Syndrome Scale (PANSS). | 3.8 scores on a scale | Standard Deviation 18.88 |
| Olanzapine | Change From Baseline in the Total Positive and Negative Syndrome Scale (PANSS). | -9.9 scores on a scale | Standard Deviation 16.83 |
p-value: <0.000195% CI: [-17.16, -8.25]ANCOVA
Secondary
Change From Baseline in Clinical Global Impression Scale (CGI-S)
The CGI-S rating scale is a 7-point global assessment with scores as follows: 1 - Not ill, 2 - Very Mild, 3 - Mild, 4 - Moderate, 5 - Marked, 6 - Severe, and 7 - Extremely Severe.
Time frame: Baseline and 6 weeks
Population: Full Analysis Set excludes subjects who didn't receive test drug or didn't have post-treatment efficacy data. The Olanzapine(OLZ) group was set as an active drug group to examine clinical position of paliperidone(PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone Extended Release (ER) (JNS007ER) | Change From Baseline in Clinical Global Impression Scale (CGI-S) | -0.4 scores on a scale | Standard Error 0.09 |
| Placebo | Change From Baseline in Clinical Global Impression Scale (CGI-S) | 0.2 scores on a scale | Standard Error 0.09 |
| Olanzapine | Change From Baseline in Clinical Global Impression Scale (CGI-S) | -0.3 scores on a scale | Standard Error 0.14 |
p-value: <0.000195% CI: [-0.84, -0.34]ANCOVA
Secondary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - General Psychopathology Subscale Score
The PANSS General Psychopathology Subscale Score assesses 16 general psychopathology symptoms. The symptoms are rated on a 7-point scale, with a range of 16 (absent) to 112 (extreme psychopathology).
Time frame: Baseline and 6 weeks
Population: Full Analysis Set excludes subjects who didn't receive test drug or didn't have post-treatment efficacy data. The Olanzapine(OLZ) group was set as an active drug group to examine clinical position of paliperidone(PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone Extended Release (ER) (JNS007ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - General Psychopathology Subscale Score | -4.1 scores on a scale | Standard Deviation 9.52 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - General Psychopathology Subscale Score | 2.2 scores on a scale | Standard Deviation 10.71 |
| Olanzapine | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - General Psychopathology Subscale Score | -4.7 scores on a scale | Standard Deviation 9 |
p-value: <0.000195% CI: [-8.58, -3.8]ANCOVA
Secondary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Negative Subscale Score
The PANSS Negative Subscale assesses seven negative-symptoms of schizophrenia. Negative symptoms represent a diminution or loss of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology).
Time frame: Baseline and 6 weeks
Population: Full Analysis Set excludes subjects who didn't receive test drug or didn't have post-treatment efficacy data. The Olanzapine(OLZ) group was set as an active drug group to examine clinical position of paliperidone(PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone Extended Release (ER) (JNS007ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Negative Subscale Score | -2.4 scores on a scale | Standard Deviation 5.05 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Negative Subscale Score | 0.0 scores on a scale | Standard Deviation 5.02 |
| Olanzapine | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Negative Subscale Score | -2.8 scores on a scale | Standard Deviation 4.27 |
p-value: <0.000195% CI: [-3.71, -1.33]ANCOVA
Secondary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Positive Subscale Score
The PANSS Positive Subscale assesses seven positive-symptoms of schizophrenia. Positive symptoms refer to an excess or distortion of normal functions. The symptoms are rated on a 7-point scale, with a range of 7 (absent) to 49 (extreme psychopathology).
Time frame: Baseline and 6 weeks
Population: Full Analysis Set excludes subjects who didn't receive test drug or didn't have post-treatment efficacy data. The Olanzapine(OLZ) group was set as an active drug group to examine clinical position of paliperidone(PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Paliperidone Extended Release (ER) (JNS007ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Positive Subscale Score | -2.6 scores on a scale | Standard Deviation 5.69 |
| Placebo | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Positive Subscale Score | 1.6 scores on a scale | Standard Deviation 5.53 |
| Olanzapine | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) - Positive Subscale Score | -2.4 scores on a scale | Standard Deviation 5.34 |
p-value: <0.000195% CI: [-5.17, -2.51]ANCOVA
Secondary
Proportion of Responders (≥30% Decrease in Total Positive and Negative Syndrome Scale [PANSS])
Responders are subjects with 30% or more reduction from baseline in total PANSS score. PANSS is a medical scale that assesses various symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). The total score is the sum of all 30 PANSS items, with a range of 30 (absent) to 210 (extreme ill).
Time frame: Baseline and 6 weeks
Population: Full Analysis Set excludes subjects who didn't receive test drug or didn't have post-treatment efficacy data. The Olanzapine(OLZ) group was set as an active drug group to examine clinical position of paliperidone(PAL) ER, and the superiority or non-inferiority of PAL ER 6mg to OLZ 10mg wasn't verified. LOCF imputation method was applied.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paliperidone Extended Release (ER) (JNS007ER) | Proportion of Responders (≥30% Decrease in Total Positive and Negative Syndrome Scale [PANSS]) | 25.4 Percentage of participants |
| Placebo | Proportion of Responders (≥30% Decrease in Total Positive and Negative Syndrome Scale [PANSS]) | 9.4 Percentage of participants |
| Olanzapine | Proportion of Responders (≥30% Decrease in Total Positive and Negative Syndrome Scale [PANSS]) | 26.1 Percentage of participants |
p-value: 0.0007Fisher Exact