Schizophrenia, Psychotic Disorders
Conditions
Keywords
Schizophrenia, Relapse, Remission, Treatment Outcome, long-acting injectable
Brief summary
The purpose of this study is to compare the effectiveness of two antipsychotic medications, Risperdal® Consta® versus Abilify®, over a 2-year treatment period in the long-term maintenance of patients with schizophrenia.
Detailed description
Although many patients with schizophrenia currently take oral antipsychotic medications, it is estimated that up to 75% of them have difficulty adhering to the daily oral regimen. Long-acting injectable formulations of antipsychotics may eliminate the need for daily medication and enhance patient compliance with the treatment regimen. The purpose of this trial is to evaluate the long-term effectiveness of Risperdal® Consta®, a long-acting injectable antipsychotic medication, versus Abilify®, an oral antipsychotic medication in patients with schizophrenia. The study will include patients, who in the investigator's opinion may benefit from a change in their current antipsychotic medication due to insufficient effectiveness, side effects or difficulty in adhering to a daily dose regimen. This is an open-label, randomized study in which patients will have an equal chance of receiving treatment for up to 2 years with Risperdal® Consta®, administered in the muscles near the hip every 2 weeks, or Abilify®, taken orally once daily. The initial dose and subsequent dose of study drug will be determined by the investigator. The patient's current oral antipsychotic medication will be decreased over the first four weeks of the study and discontinued. During the study, investigators may adjust the dose of study drug or add new antipsychotic medications to treat worsening psychotic symptoms. Patients may continue on or have added, antidepressants, mood stabilizers (except carbamazepine), sedative hypnotics, or anxiolytic medications during the study. Patients will return to the doctor's office every two weeks to receive an injection of Risperdal® Consta® or another supply of Abilify®. During certain visits, patients will be asked questions which will help the investigator determine the severity of the patient's illness, how well the study drug is working, quality of life, reasoning, memory, judgement and perception and side effects that may be associated with schizophrenia or treatment. Safety evaluations include the incidence of adverse events during the study, vital signs and clinical laboratory tests (both blood and urine). The study hypothesis is that Risperdal® Consta® is superior to Abilify® in the long-term treatment of subjects with schizophrenia as measured by time to relapse and time in remission. Treatment with Risperdal® Consta® (administered in the muscle every 2 weeks) at a dose of 25, 37.5 or 50 mg or Abilify® (administered orally daily) at a dose of 10-30 mg for 2 years. Investigators will determine the starting dose and may adjust the dosage of study drug during the study according to symptoms and treatment response.
Interventions
DRUGAbilify
10-30 mg once daily for 104 weeks
25mg, 37.5mg, or 50mg every 2 weeks for 104 weeks
Sponsors
Janssen, LP
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
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
* Patients with diagnosis of schizophrenia * Patient has had at least 2 psychotic relapses in the two years prior to study entry * patient is not adequately benefiting from their current antipsychotic medication
Exclusion criteria
* Patients that have been hospitalized or had major medication changes within 2 months of study entry * Patients currently experiencing, or who have experienced worsening of disease symptoms within 2 months of study entry * Patients currently using clozapine or carbamazepine * Patients who have undergone electroconvulsive therapy or depot antipsychotic treatment within 6 months prior to study entry * pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Relapse | Day 1 to relapse | Time to relapse was defined as the number of days from the date of first dose to the date of relapse, as determined by the Relapse Monitoring Board. |
| Time in Remission | Day 1 to last PANSS measurement | Time in remission for an individual subject was defined as the length of time (in days) that the remission criteria were maintained during the trial. Remission was defined as the simultaneous attainment of a score of 3 (mild), 2 (minimal), or 1 (absent) for all the following individual items from Positive and Negative Syndrome Scale (PANSS): delusions (P1), concept disorganization (P2), hallucinatory behavior (P3), unusual thought content (G9), mannerisms and posturing (G5), blunted affect (N1), passive/apathetic social withdrawal (N4), and lack of spontaneity and flow of conversation (N6). |
Participant flow
Recruitment details
The first patient in was on February 28, 2006; last patient out was on January 26, 2009. Enrollment occurred across multiple sites in the United States, Argentina, Chile, and India and patients were enrolled from outpatient psychiatric clinics associated with private medical practices, private clinical trial sites, and academic medical centers.
Pre-assignment details
A Screening Visit (maximum of 14 days) prior to the Treatment Phase. Baseline included psychiatric exam, lab, ECG, and schizophrenia symptom rating scale. Subjects were permitted to remain on previous psychotropic medications (i.e., antipsychotic, antidepressant, mood stabilizer, anxiolytics) up to the first 4 weeks of the Treatment Phase.
Participants by arm
| Arm | Count |
|---|---|
| Risperdal Consta 25mg, 37.5mg, or 50mg every 2 weeks injection for 104 weeks | 179 |
| Abilify 10-30 mg once daily oral for 104 weeks | 176 |
| Total | 355 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Admin issues, sponsor decision, etc. | 5 | 9 |
| Overall Study | Adverse Event | 0 | 4 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Insufficient Response | 4 | 3 |
| Overall Study | Lost to Follow-up | 18 | 10 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Withdrawal by Subject | 25 | 23 |
Baseline characteristics
| Characteristic | Risperdal Consta | Abilify | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 177 Participants | 173 Participants | 350 Participants |
| Age Continuous | 38.3 years STANDARD_DEVIATION 11.66 | 37.8 years STANDARD_DEVIATION 11.49 | 38 years STANDARD_DEVIATION 11.56 |
| Region of Enrollment India | 91 participants | 91 participants | 182 participants |
| Region of Enrollment South America | 37 participants | 33 participants | 70 participants |
| Region of Enrollment United States | 51 participants | 52 participants | 103 participants |
| Sex: Female, Male Female | 73 Participants | 70 Participants | 143 Participants |
| Sex: Female, Male Male | 106 Participants | 106 Participants | 212 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 151 / 179 | 141 / 176 |
| serious Total, serious adverse events | 31 / 179 | 35 / 176 |
Outcome results
Primary
Time in Remission
Time in remission for an individual subject was defined as the length of time (in days) that the remission criteria were maintained during the trial. Remission was defined as the simultaneous attainment of a score of 3 (mild), 2 (minimal), or 1 (absent) for all the following individual items from Positive and Negative Syndrome Scale (PANSS): delusions (P1), concept disorganization (P2), hallucinatory behavior (P3), unusual thought content (G9), mannerisms and posturing (G5), blunted affect (N1), passive/apathetic social withdrawal (N4), and lack of spontaneity and flow of conversation (N6).
Time frame: Day 1 to last PANSS measurement
Population: explanatory ITT analysis data set (eITT) contains all subjects who had at least one administration of study drug as well as at least one follow-up efficacy measurement; includes assessments while the subject is on study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Risperdal Consta | Time in Remission | 373.5 days | Standard Deviation 282.6 |
| Abilify | Time in Remission | 356.7 days | Standard Deviation 291.99 |
Comparison: Null hypothesis: there is no difference in time in remission between the two treatment groupsp-value: 0.646Wilcoxon (Mann-Whitney)
Primary
Time to Relapse
Time to relapse was defined as the number of days from the date of first dose to the date of relapse, as determined by the Relapse Monitoring Board.
Time frame: Day 1 to relapse
Population: explanatory ITT analysis data set (eITT) contains all subjects who had at least one administration of study drug as well as at least one follow-up efficacy measurement; includes assessments while the subject is on study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Risperdal Consta | Time to Relapse | 131 days |
| Abilify | Time to Relapse | 113 days |
Comparison: Null hypothesis: there is no difference in time to relapsep-value: 0.684Log Rank