Schizoaffective Disorder, Schizophrenia
Conditions
Keywords
schizophrenia, schizoaffective disorder, long acting injectable, treatment resistant
Brief summary
The purpose of this study is to look at two doses of long-acting injectable risperidone (Risperdal Consta). The study will use a usual dose of Risperdal Consta (50 mg given every two weeks) or a higher dose (75 mg-100 mg given every two weeks) to see which one is better at improving symptoms of schizophrenia or schizoaffective disorder.
Detailed description
This six month double-blind,randomized trial is designed to compare the efficacy of high dose long acting risperidone ( 75 mg-100 mg q2 weeks or its equivalent) with standard doses of long acting risperidone (≤50 mg/q 2weeks) for Total Psychopathology, positive, negative, and depressive symptoms, and cognition in patients who are considered to be poor responders by themselves, significant others, or clinicians. This will include two types of inadequately responding patients-those who are treatment resistant by research criteria (Kane et al., 1988) and those with inadequate response
Interventions
Subjects will be randomized to conventional dose Consta or high dose Consta. All of those who are randomized to the conventional Consta dose will receive it in the form of Consta at a starting dose of 50 mg q 2 weeks. Those who are randomized to high dose Consta will receive a Consta 50 mg injection plus 25 mg injection (total dose 75 mg) q 2 weeks as the starting dose.Oral risperidone will be given up to Week 4 along with the injections for both groups to provide a transition phase.At Week 6, psychopathology will be assessed with a PANSS. If no improvement from baseline is shown, the randomized dose of Consta will be increased to 100 mg q 2 weeks (given as two 50 mg injections ) for those in the high dose Consta group. The dose for those randomized to the conventional dose group will remain the same (50 mg plus placebo).
DRUGlong acting injectable risperidone, Conventional Dose Group
Study dose remains 50 mg for the length of the study.
DRUGlong acting injectable risperidone, High Dose Group
Beginning dose 75 mg. Can be increased to 100 mg at Week 6.
Sponsors
Ortho-McNeil Janssen Scientific Affairs, LLC
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed with schizophrenia or schizoaffective disorder * Able to give written informed consent. * Moderate psychosis persists although compliant with medication * Patients must have an inadequate response to two antipsychotic medications (can be risperidone, oral or long acting - but not required), at doses that are within the upper end of the standard dosage range * Patients must have a Clinical Global Impression - Severity (CGI-S) scale score at screening of at least moderate severity and a Personal and Social Performance Scale (PSP) score of 60 or below. * At the time of screening, eligible patients will be receiving or have received treatment with risperidone oral or Consta, or a combination that does not exceed 50 mg q 2 weeks of Consta or oral risperidone 8 mg/day for at least 6 weeks within seven years of study entry without satisfactory response as documented in the medical record Risperidone * Patients who have received Consta injectable medication within the specified dose range for no more than a month prior to the onset of the study will be eligible. Patients receiving mood stabilizers or antidepressants, or both, in addition to risperidone oral or Consta, will be eligible * Patients may initially be inpatients or outpatients * Females of childbearing potential will be admitted only if they are on stable birth control medication and understand that they should not get pregnant during the course of the study. * All patients must have stable housing at the current time or plans for housing following hospital discharge, if an inpatient. * Patients must be willing to receive injectable medication
Exclusion criteria
* Patients with a diagnosis other than schizophrenia or schizoaffective disorder. * Patients previously treated with doses of these agents higher than those allowed for at least six months and who failed to have an adequate response will be excluded * Patients currently taking clozapine or have failed an adequate trial of clozapine which lasted at least 3 months * Pregnant females. Females who are currently breastfeeding will be excluded. * Patients with a diagnosis of substance dependence at screening or up to one year prior to enrollment. * Patient with worse than mild tardive dyskinesia or history of marked Extrapyramidal Symptoms (EPS) at screening * Patients who have had neuroleptic malignant syndrome * Patients with a history of galactorrhea * Patients with uncontrolled medical condition(s) * Patients with a history of non-compliance to oral or injectable medication. * Patients unwilling to have injectable medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | six months | The mean (SEM) of Positive and Negative Syndrome Scale (PANSS) The Positive and Negative Syndrome Scale (PANSS) is a 30-item questionnaire used to assess the severity of symptoms in schizophrenia. It's considered a gold standard for measuring symptom change in antipsychotic trials and other research. The PANSS is divided into three subscales: positive symptoms, negative symptoms, and general psychopathology. Each item is rated on a 7-point scale, ranging from absent to extreme. Therefore, the minimum possible score of 0 and maximum possible score is 210, but those scores may never be seen in a practical setting. If the score reduces over time that indicates improvement of the symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive and Negative Syndrome Scale (PANSS) Positive Scale | six months | Positive and Negative Syndrome Scale (PANSS) Positive scale: Consists of sum of 7 items, so the score can range from 0 - 49. Improvement means lower scores over time |
| Positive and Negative Syndrome Scale (PANSS) Negative Scale | six months | Positive and Negative Syndrome Scale (PANSS) Negative scale: Consists of sum of 7 items, so the score can range from 0 - 49. Improvement means lower scores over time |
Countries
United States
Participant flow
Pre-assignment details
One hundred sixty-nine patients who met Diagnostic and Statistical Manual (DSM-IV) criteria for schizophrenia or schizoaffective disorder were screened, and 160 patients were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Conventional Dose All of those who are randomized to the conventional Consta dose will receive it in the form of Consta at a starting dose of 50 mg q 2 weeks (given as two injections - active 50 mg plus placebo injection).
long-acting injectable risperidone, Conventional Dose Group: The study dose remains 50 mg for the length of the study. | 82 |
| High Dose Group Those who are randomized to high dose Consta will receive Consta 50 mg injection plus 25 mg injection (total dose 75 mg) q 2 weeks as the starting dose after consent.
long-acting injectable risperidone, High Dose Group: Beginning dose 75 mg. Can be increased to 100 mg at Week 6. | 78 |
| Total | 160 |
Baseline characteristics
| Characteristic | Conventional Dose | High Dose Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 82 Participants | 78 Participants | 160 Participants |
| Age, Continuous | 39.2 years STANDARD_DEVIATION 10.6 | 41 years STANDARD_DEVIATION 11.4 | 40.1 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 6 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 76 Participants | 72 Participants | 148 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 82 participants | 78 participants | 160 participants |
| Sex: Female, Male Female | 22 Participants | 22 Participants | 44 Participants |
| Sex: Female, Male Male | 60 Participants | 56 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 78 |
| other Total, other adverse events | 14 / 82 | 13 / 78 |
| serious Total, serious adverse events | 2 / 82 | 5 / 78 |
Outcome results
Primary
Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks.
The mean (SEM) of Positive and Negative Syndrome Scale (PANSS) The Positive and Negative Syndrome Scale (PANSS) is a 30-item questionnaire used to assess the severity of symptoms in schizophrenia. It's considered a gold standard for measuring symptom change in antipsychotic trials and other research. The PANSS is divided into three subscales: positive symptoms, negative symptoms, and general psychopathology. Each item is rated on a 7-point scale, ranging from absent to extreme. Therefore, the minimum possible score of 0 and maximum possible score is 210, but those scores may never be seen in a practical setting. If the score reduces over time that indicates improvement of the symptoms.
Time frame: six months
Population: patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Conventional Dose | Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | 6 Weeks | 80.0 score on a scale | Standard Error 1.3 |
| Conventional Dose | Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | 18 Weeks | 72.3 score on a scale | Standard Error 1.4 |
| Conventional Dose | Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | 12 Weeks | 74.2 score on a scale | Standard Error 1.3 |
| Conventional Dose | Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | 24 Weeks | 70.9 score on a scale | Standard Error 1.4 |
| Conventional Dose | Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | Baseline | 89.0 score on a scale | Standard Error 1.2 |
| High Dose Group | Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | 24 Weeks | 72.0 score on a scale | Standard Error 1.4 |
| High Dose Group | Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | Baseline | 89.7 score on a scale | Standard Error 1.3 |
| High Dose Group | Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | 6 Weeks | 80.8 score on a scale | Standard Error 1.3 |
| High Dose Group | Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | 12 Weeks | 78.0 score on a scale | Standard Error 1.4 |
| High Dose Group | Total Positive and Negative Syndrome Scale (PANSS) Score Between Baseline and 24 Weeks. | 18 Weeks | 74.0 score on a scale | Standard Error 1.4 |
Secondary
Positive and Negative Syndrome Scale (PANSS) Negative Scale
Positive and Negative Syndrome Scale (PANSS) Negative scale: Consists of sum of 7 items, so the score can range from 0 - 49. Improvement means lower scores over time
Time frame: six months
Population: patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Conventional Dose | Positive and Negative Syndrome Scale (PANSS) Negative Scale | PANSS Negative 6 Weeks | 19.8 score on a scale | Standard Error 0.4 |
| Conventional Dose | Positive and Negative Syndrome Scale (PANSS) Negative Scale | PANSS Negative 18 Weeks | 17.9 score on a scale | Standard Error 0.4 |
| Conventional Dose | Positive and Negative Syndrome Scale (PANSS) Negative Scale | PANSS Negative 12 Weeks | 18.4 score on a scale | Standard Error 0.4 |
| Conventional Dose | Positive and Negative Syndrome Scale (PANSS) Negative Scale | PANSS Negative 24 Weeks | 17.9 score on a scale | Standard Error 0.4 |
| Conventional Dose | Positive and Negative Syndrome Scale (PANSS) Negative Scale | PANSS Negative Baseline | 21.0 score on a scale | Standard Error 0.4 |
| High Dose Group | Positive and Negative Syndrome Scale (PANSS) Negative Scale | PANSS Negative 24 Weeks | 18.5 score on a scale | Standard Error 0.5 |
| High Dose Group | Positive and Negative Syndrome Scale (PANSS) Negative Scale | PANSS Negative Baseline | 21.2 score on a scale | Standard Error 0.4 |
| High Dose Group | Positive and Negative Syndrome Scale (PANSS) Negative Scale | PANSS Negative 6 Weeks | 19.5 score on a scale | Standard Error 0.4 |
| High Dose Group | Positive and Negative Syndrome Scale (PANSS) Negative Scale | PANSS Negative 12 Weeks | 19.2 score on a scale | Standard Error 0.5 |
| High Dose Group | Positive and Negative Syndrome Scale (PANSS) Negative Scale | PANSS Negative 18 Weeks | 18.6 score on a scale | Standard Error 0.4 |
Secondary
Positive and Negative Syndrome Scale (PANSS) Positive Scale
Positive and Negative Syndrome Scale (PANSS) Positive scale: Consists of sum of 7 items, so the score can range from 0 - 49. Improvement means lower scores over time
Time frame: six months
Population: patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Conventional Dose | Positive and Negative Syndrome Scale (PANSS) Positive Scale | PANSS Positive 18 Weeks | 18.2 score on a scale | Standard Error 0.5 |
| Conventional Dose | Positive and Negative Syndrome Scale (PANSS) Positive Scale | PANSS Positive Baseline | 24.0 score on a scale | Standard Error 0.4 |
| Conventional Dose | Positive and Negative Syndrome Scale (PANSS) Positive Scale | PANSS Positive 6 Weeks | 20.8 score on a scale | Standard Error 0.5 |
| Conventional Dose | Positive and Negative Syndrome Scale (PANSS) Positive Scale | PANSS Positive 12 Weeks | 20.0 score on a scale | Standard Error 0.5 |
| Conventional Dose | Positive and Negative Syndrome Scale (PANSS) Positive Scale | PANSS Positive 24 Weeks | 18.1 score on a scale | Standard Error 0.5 |
| High Dose Group | Positive and Negative Syndrome Scale (PANSS) Positive Scale | PANSS Positive 24 Weeks | 18.1 score on a scale | Standard Error 0.5 |
| High Dose Group | Positive and Negative Syndrome Scale (PANSS) Positive Scale | PANSS Positive 12 Weeks | 20.0 score on a scale | Standard Error 0.5 |
| High Dose Group | Positive and Negative Syndrome Scale (PANSS) Positive Scale | PANSS Positive Baseline | 24.2 score on a scale | Standard Error 0.5 |
| High Dose Group | Positive and Negative Syndrome Scale (PANSS) Positive Scale | PANSS Positive 18 Weeks | 19.1 score on a scale | Standard Error 0.5 |
| High Dose Group | Positive and Negative Syndrome Scale (PANSS) Positive Scale | PANSS Positive 6 Weeks | 21.4 score on a scale | Standard Error 0.5 |