Psychotic Disorders, Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
antipsychotic, paliperidone ER, liver disease, Schizophrenia, Schizoaffective Disorder, Invega
Brief summary
The purpose of this study is to evaluate the tolerability and safety of paliperidone ER (extended-release) in doses between 3 milligrams per day and 12 milligrams per day in the treatment of patients with schizophrenia or schizoaffective disorder and liver disease.
Detailed description
Patients with schizophrenia or schizoaffective disorder commonly have other conditions that may affect the liver, such as alcohol abuse and/or chronic liver infections (hepatitis). Although single-dose studies in patients with liver disease are conducted to test the safety of medications, there is less information about the safety of treatment with medications for schizophrenia in this at-risk population of patients with schizophrenia or schizoaffective disorder and liver disease. This 9-week study is open-label (both patient and investigators know what study drug and dose of study drug the patient is taking) and has 2 phases. During Phase 1, which lasts 4 weeks, patients will continue to take whatever medication they are already taking for schizophrenia (TAU, or treatment as usual). During the first week of Phase 2, patients will receive decreasing doses of TAU and increasing doses of paliperidone ER. For the rest of Phase 2, which lasts 4 more weeks, patients will take paliperidone ER in doses between 3 mg/day and 12 mg/day, as prescribed by the study doctor. This study will evaluate adverse events and will use several scales and tests to measure the effectiveness of paliperidone ER in patients with an established diagnosis of schizophrenia or schizoaffective disorder and liver disease. Study assessments include the PANSS (Positive and Negative Symptom Scale for Schizophrenia), CGI (Clinical Global Impression scale), MSQ (Medication Satisfaction Questionnaire), sleep VAS (Visual Analog Scale), SF-36 (Short Form 36 Health Survey), and PSP (Personal and Social Performance Scale). Each assessment will be performed at least two times during the course of the study, but some assessments will be done more frequently. Visits are scheduled every 1 to two weeks during the 9 week study. The hypothesis is that paliperidone ER can be used safely in patients with schizophrenia or schizoaffective disorder who also have identified liver disease. During Phase 1 of the study, patients will continue to take whatever medication they are already taking for schizophrenia (TAU, or treatment as usual) for 4 weeks. For the first week of Phase 2, patients will receive decreasing doses of TAU. During Phase 2, patients will take paliperidone ER in doses between 3 milligrams per day and 12 milligrams per day by mouth for 5 weeks.
Interventions
DRUGTreatment as usual (TAU), Paliperidone ER
Treatment as usual is the subject's current antipsychotic and doses for 4 weeks; TAU AND Paliperidone ER - per site investigator for 1 week; Paliperidone ER 6mg once daily for 1 week; Paliperidone ER-3 to 12mg tablets once daily for 4 weeks
Sponsors
Ortho-McNeil Janssen Scientific Affairs, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women must be postmenopausal for at least 1 year, surgically sterile, abstinent, or agree to practice an effective method of birth control if they are sexually active before entry and throughout the study, and must also have a negative urine pregnancy test at Screening * Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder * Must have identified current, stable liver disease (e.g., viral hepatitis, alcoholic cirrhosis) * Child-Pugh class A or B (total score \< 10)
Exclusion criteria
* Not able to swallow the study medication whole with the aid of water * Not currently meeting criteria for any other Axis I diagnosis, including a DSM-IV diagnosis of Bipolar Disorder * Not using alcohol in the previous 2 weeks or meeting the DSM-IV criteria for substance abuse or dependence or alcohol abuse or dependence in the 6 months before study entry * Not experiencing severe liver disease or an acute exacerbation of the underlying liver disease (Child-Pugh total score \>=10) * No evidence of severe hepatic decompensation within the previous 3 months, such as: ascites not controlled with diuretics, peritonitis, portal hypertension or gross hepatic encephalopathy (eg, somnolence, stupor, coma)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Difference in the Incidence of Any Adverse Events When Patients Switch Their Antipsychotic From Treatment as Usual (TAU) to Paliperidone ER | Day 1 - Day 62 | Adverse Event summary for both serious adverse events and other adverse events. Please see the Clinical Study Report Synopsis for results on this primary outcome measure or the AE section for a detailed breakdown of each adverse event preferred term in both categories. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive and Negative Symptoms of Schizophrenia (PANSS) Change From Baseline | Day 1 - Day 62 | The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale (1=Absent, 2=Minimal, 3=Mild, 4=Moderate, 5=Moderate/Severe, 6=Severe, 7=Extreme).The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate more severe neuropsychiatric symptoms of schizophrenia. |
| Clinical Global Impression of Severity (CGI-S) Change From Baseline | Day 1 - Day 62 | The CGI-S (range 1-7) is a standardized, clinician-rated assessment to rate the severity of illness of the patient. The clinician assessed the severity of illness using the following categories: 1 = normal, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill. The minimum score is 1 and maximum score is 7, with higher scores indicating more severe illness. |
| Personal and Social Performance Score (PSP) Change From Baseline | Day 1 - Day 62 | The PSP (range 1-100) is a validated clinician-rated assessment of functioning. Four areas of functioning (socially useful activities, personal/social relationships, self-care, disturbing/aggressive behaviors) are assessed on a 6-point scale (0=absent to 5=very severe). A transformed score from 1 to 100 is generated from the raw score based on the clinical interpretation of the scores generated in the 4 areas of functioning, with a higher transformed score indicating better function. |
Countries
United States
Participant flow
Recruitment details
One-hundred-twenty-one (121) participants were enrolled but only 114 entered Phase 1 of the study (5 participants enrolled twice and only had their first entrance included and 2 participants did not sign the required HIPAA form).
Participants by arm
| Arm | Count |
|---|---|
| Study Treatment Phase 1; Day 1 through Day 27: Patients took therapy for schizophrenia as prescribed before study entry (referred to treatment as usual abbreviated as TAU) for 4 weeks. Phase 2; Day 28 through Day 62: The dose of TAU was then tapered (reduced and stopped) over a 1-week period and treatment started with paliperidone extended-release (ER) tablets, 6 mg, orally (by mouth) once daily followed by 4 weeks of paliperidone ER, 3-12 mg once daily as monotherapy (treatment with Paliperidone ER alone). | 84 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase I | Adverse Event | 3 |
| Phase I | (diagnosis) | 3 |
| Phase I | (eligibility) | 8 |
| Phase I | Lost to Follow-up | 7 |
| Phase I | (PI decision) | 1 |
| Phase I | (protocol violation) | 1 |
| Phase I | Withdrawal by Subject | 6 |
| Phase II | Adverse Event | 2 |
| Phase II | Lack of Efficacy | 1 |
| Phase II | Lost to Follow-up | 5 |
| Phase II | Subject non-compliance | 2 |
| Phase II | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Study Treatment |
|---|---|
| Age, Continuous | 48.9 years STANDARD_DEVIATION 6.73 |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 57 Participants |
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 | 27 / 84 | 43 / 84 | 32 / 114 |
| serious Total, serious adverse events | 0 / 84 | 2 / 84 | 2 / 114 |
Outcome results
Primary
The Difference in the Incidence of Any Adverse Events When Patients Switch Their Antipsychotic From Treatment as Usual (TAU) to Paliperidone ER
Adverse Event summary for both serious adverse events and other adverse events. Please see the Clinical Study Report Synopsis for results on this primary outcome measure or the AE section for a detailed breakdown of each adverse event preferred term in both categories.
Time frame: Day 1 - Day 62
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study Treatment | The Difference in the Incidence of Any Adverse Events When Patients Switch Their Antipsychotic From Treatment as Usual (TAU) to Paliperidone ER | Serious Adverse Events | 0 Participants |
| Study Treatment | The Difference in the Incidence of Any Adverse Events When Patients Switch Their Antipsychotic From Treatment as Usual (TAU) to Paliperidone ER | Other Adverse Events | 27 Participants |
| Paliperidone ER Phase | The Difference in the Incidence of Any Adverse Events When Patients Switch Their Antipsychotic From Treatment as Usual (TAU) to Paliperidone ER | Serious Adverse Events | 2 Participants |
| Paliperidone ER Phase | The Difference in the Incidence of Any Adverse Events When Patients Switch Their Antipsychotic From Treatment as Usual (TAU) to Paliperidone ER | Other Adverse Events | 43 Participants |
Secondary
Clinical Global Impression of Severity (CGI-S) Change From Baseline
The CGI-S (range 1-7) is a standardized, clinician-rated assessment to rate the severity of illness of the patient. The clinician assessed the severity of illness using the following categories: 1 = normal, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, 7 = among the most extremely ill. The minimum score is 1 and maximum score is 7, with higher scores indicating more severe illness.
Time frame: Day 1 - Day 62
Population: Efficacy Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Treatment | Clinical Global Impression of Severity (CGI-S) Change From Baseline | Day 13 (n=78) | -0.1 Scores on a scale | Standard Deviation 0.39 |
| Study Treatment | Clinical Global Impression of Severity (CGI-S) Change From Baseline | Day 27 Paliperidone ER Baseline (n=79) | -0.1 Scores on a scale | Standard Deviation 0.37 |
| Study Treatment | Clinical Global Impression of Severity (CGI-S) Change From Baseline | Day 48 (n=74) | -0.3 Scores on a scale | Standard Deviation 0.6 |
| Study Treatment | Clinical Global Impression of Severity (CGI-S) Change From Baseline | Day 62 (n=77) | -0.4 Scores on a scale | Standard Deviation 0.65 |
| Study Treatment | Clinical Global Impression of Severity (CGI-S) Change From Baseline | Post Day 27 Endpoint (n=79) | -0.4 Scores on a scale | Standard Deviation 0.67 |
Secondary
Personal and Social Performance Score (PSP) Change From Baseline
The PSP (range 1-100) is a validated clinician-rated assessment of functioning. Four areas of functioning (socially useful activities, personal/social relationships, self-care, disturbing/aggressive behaviors) are assessed on a 6-point scale (0=absent to 5=very severe). A transformed score from 1 to 100 is generated from the raw score based on the clinical interpretation of the scores generated in the 4 areas of functioning, with a higher transformed score indicating better function.
Time frame: Day 1 - Day 62
Population: Includes participants in the efficacy analysis set for with PSP scores available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Treatment | Personal and Social Performance Score (PSP) Change From Baseline | Day 27 Paliperidone ER Baseline (n=78) | 1.2 Scores on a scale | Standard Deviation 7.25 |
| Study Treatment | Personal and Social Performance Score (PSP) Change From Baseline | Day 62 (n=76) | 2.8 Scores on a scale | Standard Deviation 7.23 |
Secondary
Positive and Negative Symptoms of Schizophrenia (PANSS) Change From Baseline
The PANSS is a 30-item scale (range 30-210) designed to assess various symptoms of schizophrenia including delusions, grandiosity, blunted affect, poor attention, and poor impulse control. The 30 symptoms are rated on a 7-point scale (1=Absent, 2=Minimal, 3=Mild, 4=Moderate, 5=Moderate/Severe, 6=Severe, 7=Extreme).The PANSS total score consists of the sum of all 30 PANSS items. Higher scores indicate more severe neuropsychiatric symptoms of schizophrenia.
Time frame: Day 1 - Day 62
Population: Efficacy Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study Treatment | Positive and Negative Symptoms of Schizophrenia (PANSS) Change From Baseline | Day 27 (n=79) | -1.7 Scores on a scale | Standard Deviation 7.35 |
| Study Treatment | Positive and Negative Symptoms of Schizophrenia (PANSS) Change From Baseline | Day 48 (n=74) | -5.4 Scores on a scale | Standard Deviation 8.72 |
| Study Treatment | Positive and Negative Symptoms of Schizophrenia (PANSS) Change From Baseline | Day 62 (n=77) | -7.2 Scores on a scale | Standard Deviation 9.91 |
| Study Treatment | Positive and Negative Symptoms of Schizophrenia (PANSS) Change From Baseline | Post Day 27 Endpoint (n=79) | -7.6 Scores on a scale | Standard Deviation 10.43 |