Schizophrenia
Conditions
Keywords
Schizophrenia, Paliperidone Extended-Release
Brief summary
The purpose of the study is to explore the maintained efficacy, tolerability, and safety of flexibly dosed paliperidone extended-release (ER) in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self) previously unsuccessfully treated with other oral atypical antipsychotic medication.
Detailed description
This is an open-label (all people know the identity of the intervention), non-randomized (the study drug is not assigned by chance), single arm, multicenter (when more than one hospital or medical school team work on a medical research study), 24-week study. Participants can be transitioned to an effective dose of paliperidone ER from any oral antipsychotic medication without the need for titration due to lack of efficacy, lack of tolerability or safety, lack of compliance or other reason. A transition period of maximum 4 weeks will be allowed. Throughout the study, participants will receive flexible dose of 3 to 12 milligram (mg) of paliperidone once daily orally for 24 weeks. Dose adjustment will be done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug. Assessments of efficacy will be performed at screening and after 2, 4, 12 and 24 weeks. Efficacy will primarily be evaluated by means of Positive and Negative Syndrome Scale (PANSS). Participants' safety will also be monitored throughout the study.
Interventions
DRUGPaliperidone ER
Participants will receive paliperidone ER tablet in dose range of 3 to12 milligram (mg) per day orally once daily for 24 weeks as per Investigator's discretion based on the individual participant's clinical response to and tolerability of the study drug.
Sponsors
Johnson & Johnson Taiwan Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant meets the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for schizophrenia * Participant has been given an adequate dose of an appropriate oral atypical antipsychotic for an adequate period of time prior to enrollment, but previous treatment is considered unsuccessful due to one or more of the following reasons: lack of efficacy, lack of tolerability or safety, lack of compliance and/or other reasons to switch to another antipsychotic medication * Participant or their legally acceptable representatives must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study * Female participants must be postmenopausal for at least 1 year, surgically sterile, abstinent, or, if sexually active, agree to practice an effective method of birth control before entry and throughout the study and must also have a negative urine pregnancy test at screening * Male or female, aged greater than or equal to 18 years
Exclusion criteria
* Participants on clozapine, any conventional depot neuroleptic or Risperdal CONSTA during the last 3 months * Participants with serious unstable medical condition, including known clinically relevant laboratory abnormalities * Participants with history or current symptoms of tardive dyskinesia (twitching or jerking movements that you cannot control in your face, tongue, or other parts of your body) * Participants with history of neuroleptic malignant syndrome (high fever, rigid muscles, shaking, confusion, sweating more than usual, increased heart rate or blood pressure, or muscle pain or weakness) * Participants with a current use or known history (over the past 6 months) of substance dependence except for nicotine, caffeine, and betal nut according to DSM-IV Criteria
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24 | Baseline, Week 24 | The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self). The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent) to 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least 20 Percent Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score | Up to Week 24 | The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self). The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent) to 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity. |
| Change From Baseline in Total Personal and Social Performance (PSP) Score at Week 24 | Baseline, Week 24 | The PSP is 100-point validated clinician-rated scale that assesses degree of difficulty in 4 areas of functioning: socially useful activities, personal and social relationships, self-care, disturbing and aggressive behaviors rated on 6-point scale (1=absent to 6=very severe).Total transformed score from 1 to 100 is generated from raw score based on clinical interpretation of scores generated in 4 areas of functioning, with higher transformed score indicating better function. Total score is divided into 3 levels: 71-100 (mild difficulty); 31-70 (marked difficulty) and 1-30 (severe difficulty). |
| Change From Baseline in Global Assessment of Functioning (GAF) Score at Week 24 | Baseline, Week 24 | The GAF is a 100-point tool rating overall psychological, social and occupational functioning of adults. The higher score range (91-100) refers to a superior functioning in a wide range of activities, and absence of symptoms. The lower score range (1-10) refers to persistent danger of severely hurting self or others; or persistent inability to maintain minimum personal hygiene; or serious suicidal act with clear expectation of death. |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | Baseline, Week 24 | The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Marder PANSS subscales include positive symptoms subscale consisting of 8 items with total score range of 8-56; negative symptoms subscale and disorganized thoughts subscale, each consisting of 7 items with total score range of 7-49; and uncontrolled hostility/excitement (UH/E) subscale and anxiety/depression subscale, each consisting of 4 items with total score range of 4-28. Higher score indicates greater severity. |
| Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Week 24 | Baseline, Week 24 | The SF-36 is a health status survey with 36 questions measuring 8 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) that are subsequently aggregated into 2 summary scales, Physical Component Summary (PCS) and Mental Component Summary (MCS). Each item is scored into on a 0-100 range so that the lowest and highest possible scores are set at 0 and 100, respectively. All items are scored so that a high score defines a more favorable health state. |
| Number of Participants With Satisfaction With the Study Treatment | Week 24 | Participants assessed their satisfaction with paliperidone ER on a 5-point scale (very good, good, moderate, poor or very poor). |
| Change From Baseline in Sleep Quality and Daytime Drowsiness Score at Week 24 | Baseline, Week 24 | The Sleep Quality and Daytime Drowsiness evaluation scale is a self-administered scale that rates quality of sleep and daytime drowsiness. Participants indicated on a 5 point scale how well they have slept in the previous 7 days, score ranging from 1 (very badly) to 5 (very well) and how often they have felt drowsy within the previous 7 days, score ranging from 1 (not at all) to 5 (all the time). |
| Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 24 | Baseline, Week 24 | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Paliperidone Extended Release (ER) Participants received flexible dose of 3 to 12 milligram (mg) of paliperidone ER once daily orally for 24 weeks. Dose adjustment was done as per Investigator's discretion based upon participant's clinical response to and tolerability of the study drug. | 299 |
| Total | 299 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 19 |
| Overall Study | Ineligible to continue | 8 |
| Overall Study | Insufficient Response | 26 |
| Overall Study | Lost to Follow-up | 16 |
| Overall Study | Non-compliant | 9 |
| Overall Study | Other | 18 |
| Overall Study | Withdrawal by Subject | 25 |
Baseline characteristics
| Characteristic | Paliperidone Extended Release (ER) |
|---|---|
| Age, Continuous | 40.1 years STANDARD_DEVIATION 11.85 |
| Sex: Female, Male Female | 162 Participants |
| Sex: Female, Male Male | 137 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 180 / 299 |
| serious Total, serious adverse events | 11 / 299 |
Outcome results
Primary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24
The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self). The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent) to 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity.
Time frame: Baseline, Week 24
Population: Intent-to-treat (ITT) population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Missing data was imputed using last observation carried forward (LOCF). Here, 'n' signifies those participants who were evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24 | Baseline (n=297) | 72.4 Units on a scale | Standard Deviation 21.1 |
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24 | Change at Week 24 (n=281) | -6.9 Units on a scale | Standard Deviation 17.3 |
Secondary
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 24
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.
Time frame: Baseline, Week 24
Population: ITT population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Missing data was imputed using LOCF. Here, 'n' signifies those participants who were evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Extended Release (ER) | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 24 | Baseline (n=297) | 4.3 Units on a scale | Standard Deviation 1.1 |
| Paliperidone Extended Release (ER) | Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Week 24 | Change at Week 24 (n=279) | -0.5 Units on a scale | Standard Deviation 1.1 |
Secondary
Change From Baseline in Global Assessment of Functioning (GAF) Score at Week 24
The GAF is a 100-point tool rating overall psychological, social and occupational functioning of adults. The higher score range (91-100) refers to a superior functioning in a wide range of activities, and absence of symptoms. The lower score range (1-10) refers to persistent danger of severely hurting self or others; or persistent inability to maintain minimum personal hygiene; or serious suicidal act with clear expectation of death.
Time frame: Baseline, Week 24
Population: ITT population: all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Missing data was imputed using LOCF. Here 'N' (Number of Participants Analyzed) signifies number of participants who were evaluable for this measure. 'n' signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Extended Release (ER) | Change From Baseline in Global Assessment of Functioning (GAF) Score at Week 24 | Baseline (n=273) | 48.9 Units on a scale | Standard Deviation 14.7 |
| Paliperidone Extended Release (ER) | Change From Baseline in Global Assessment of Functioning (GAF) Score at Week 24 | Change at Week 24 (n=246) | 5.8 Units on a scale | Standard Deviation 15.2 |
Secondary
Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24
The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia. The symptoms are rated on a 7-point scale from 1 (absent) to 7 (extreme psychopathology). Marder PANSS subscales include positive symptoms subscale consisting of 8 items with total score range of 8-56; negative symptoms subscale and disorganized thoughts subscale, each consisting of 7 items with total score range of 7-49; and uncontrolled hostility/excitement (UH/E) subscale and anxiety/depression subscale, each consisting of 4 items with total score range of 4-28. Higher score indicates greater severity.
Time frame: Baseline, Week 24
Population: ITT population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Missing data was imputed using LOCF. Here, 'n' signifies those participants who were evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | Positive symptoms: Baseline (n=297) | 21.6 Units on a scale | Standard Deviation 7.2 |
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | Positive symptoms:Change at Week 24 (n=281) | -2.2 Units on a scale | Standard Deviation 5.6 |
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | Negative symptoms: Baseline (n=297) | 17.0 Units on a scale | Standard Deviation 7 |
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | Negative symptoms:Change at Week 24 (n=281) | -1.7 Units on a scale | Standard Deviation 4.4 |
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | Disorganized thoughts: Baseline (n=297) | 16.7 Units on a scale | Standard Deviation 6.6 |
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | Disorganized thoughts: Change at Week 24 (n=281) | -1.4 Units on a scale | Standard Deviation 4.4 |
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | UH/E: Baseline (n=297) | 7.5 Units on a scale | Standard Deviation 3.3 |
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | UH/E: Change at Week 24 (n=281) | -0.5 Units on a scale | Standard Deviation 3.9 |
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | Anxiety/depression: Baseline (n=297) | 9.7 Units on a scale | Standard Deviation 3.8 |
| Paliperidone Extended Release (ER) | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Marder Subscale Scores at Week 24 | Anxiety/depression:Change at Week 24(n=281) | -1.1 Units on a scale | Standard Deviation 3.5 |
Secondary
Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Week 24
The SF-36 is a health status survey with 36 questions measuring 8 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) that are subsequently aggregated into 2 summary scales, Physical Component Summary (PCS) and Mental Component Summary (MCS). Each item is scored into on a 0-100 range so that the lowest and highest possible scores are set at 0 and 100, respectively. All items are scored so that a high score defines a more favorable health state.
Time frame: Baseline, Week 24
Population: ITT population: all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Missing data was imputed using LOCF. Here 'N' (Number of Participants Analyzed) signifies number of participants who were evaluable for this measure. 'n' signifies those participants who were evaluable at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Extended Release (ER) | Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Week 24 | PCS: Baseline (n=293) | 61.3 Units on a scale | Standard Deviation 19.8 |
| Paliperidone Extended Release (ER) | Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Week 24 | PCS: Change at Week 24 (n=225) | 0.6 Units on a scale | Standard Deviation 16.1 |
| Paliperidone Extended Release (ER) | Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Week 24 | MCS: Baseline (n=295) | 53.1 Units on a scale | Standard Deviation 21.5 |
| Paliperidone Extended Release (ER) | Change From Baseline in Short-Form 36 Health Survey (SF-36) Score at Week 24 | MCS: Change at Week 24 (n=228) | 2.0 Units on a scale | Standard Deviation 18.4 |
Secondary
Change From Baseline in Sleep Quality and Daytime Drowsiness Score at Week 24
The Sleep Quality and Daytime Drowsiness evaluation scale is a self-administered scale that rates quality of sleep and daytime drowsiness. Participants indicated on a 5 point scale how well they have slept in the previous 7 days, score ranging from 1 (very badly) to 5 (very well) and how often they have felt drowsy within the previous 7 days, score ranging from 1 (not at all) to 5 (all the time).
Time frame: Baseline, Week 24
Population: ITT population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Here, 'n' signifies those participants who were evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Extended Release (ER) | Change From Baseline in Sleep Quality and Daytime Drowsiness Score at Week 24 | Quality of sleep: Baseline (n=297) | 3.2 Units on a scale | Standard Deviation 1 |
| Paliperidone Extended Release (ER) | Change From Baseline in Sleep Quality and Daytime Drowsiness Score at Week 24 | Quality of sleep:Change at Week 24 (n=278) | 0.1 Units on a scale | Standard Deviation 1.1 |
| Paliperidone Extended Release (ER) | Change From Baseline in Sleep Quality and Daytime Drowsiness Score at Week 24 | Daytime drowsiness: Baseline (n=297) | 2.6 Units on a scale | Standard Deviation 1 |
| Paliperidone Extended Release (ER) | Change From Baseline in Sleep Quality and Daytime Drowsiness Score at Week 24 | Daytime drowsiness:Change at Week 24 (n=278) | -0.3 Units on a scale | Standard Deviation 1.2 |
Secondary
Change From Baseline in Total Personal and Social Performance (PSP) Score at Week 24
The PSP is 100-point validated clinician-rated scale that assesses degree of difficulty in 4 areas of functioning: socially useful activities, personal and social relationships, self-care, disturbing and aggressive behaviors rated on 6-point scale (1=absent to 6=very severe).Total transformed score from 1 to 100 is generated from raw score based on clinical interpretation of scores generated in 4 areas of functioning, with higher transformed score indicating better function. Total score is divided into 3 levels: 71-100 (mild difficulty); 31-70 (marked difficulty) and 1-30 (severe difficulty).
Time frame: Baseline, Week 24
Population: ITT population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Missing data was imputed using LOCF. Here, 'n' signifies those participants who were evaluable for this outcome measure at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Paliperidone Extended Release (ER) | Change From Baseline in Total Personal and Social Performance (PSP) Score at Week 24 | Baseline (n=297) | 54.5 Units on a scale | Standard Deviation 13.8 |
| Paliperidone Extended Release (ER) | Change From Baseline in Total Personal and Social Performance (PSP) Score at Week 24 | Change at Week 24 (n=269) | 3.4 Units on a scale | Standard Deviation 12.7 |
Secondary
Number of Participants With Satisfaction With the Study Treatment
Participants assessed their satisfaction with paliperidone ER on a 5-point scale (very good, good, moderate, poor or very poor).
Time frame: Week 24
Population: ITT population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Here 'N' (Number of Participants Analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Paliperidone Extended Release (ER) | Number of Participants With Satisfaction With the Study Treatment | Very good | 11 Participants |
| Paliperidone Extended Release (ER) | Number of Participants With Satisfaction With the Study Treatment | Good | 83 Participants |
| Paliperidone Extended Release (ER) | Number of Participants With Satisfaction With the Study Treatment | Moderate | 83 Participants |
| Paliperidone Extended Release (ER) | Number of Participants With Satisfaction With the Study Treatment | Poor | 49 Participants |
| Paliperidone Extended Release (ER) | Number of Participants With Satisfaction With the Study Treatment | Very poor | 11 Participants |
Secondary
Percentage of Participants With at Least 20 Percent Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score
The PANSS is a 30-item scale to assess the neuropsychiatric symptoms of schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self). The PANSS provides a total score and scores for 3 subscales, the positive subscale (7 items), the negative subscale (7 items), and the general psychopathology subscale (16 items), each item scored on a scale of 1 (absent) to 7 (extreme). The total score ranges from 30 to 210 and higher score indicates greater severity.
Time frame: Up to Week 24
Population: ITT population included all participants who received at least 1 dose of study drug and had at least one post-baseline assessment. Here 'N' (Number of Participants Analyzed) signifies participants evaluable for this measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Paliperidone Extended Release (ER) | Percentage of Participants With at Least 20 Percent Improvement in Positive and Negative Syndrome Scale (PANSS) Total Score | 31.3 Percentage of participants |