Schizophrenia
Conditions
Keywords
Schizophrenia, Risperidone, Risperdal Consta, Oral antipsychotic
Brief summary
The purpose of this study is to evaluate the long-term treatment efficacy, and safety of risperidone long-acting injection in participants with schizophrenia (psychiatric disorder with symptoms of emotional instability, detachment from reality, often with delusions and hallucinations, and withdrawal into the self).
Detailed description
This is an open-label (all people know the identity of the intervention), multi-center (conducted in more than one center), prospective (study following participants forward in time) and observational study of risperidone long-acting injection in participants with schizophrenia. The study consists of 2 parts: Screening (that is, 28 days before study commences on Day 1) and Treatment (that is, Week 1-24). All the eligible participants (after risperidone intolerance test during screening) will be receiving risperidone as intramuscular injection (injection of a substance into a muscle) at a dose of, either 25 milligram (mg), 37.5 mg or 50 mg every two weeks. Efficacy of the participants will be primarily evaluated through Positive and Negative Syndrome Scale. Participants' safety will be monitored throughout the study.
Interventions
DRUGRisperidone
This is an observational study. Risperidone will be administered as intramuscular injection at a starting dose of either 25 milligram (mg) or 37.5 mg or 50 mg (starting dose will be decided on the basis of the disease severity), every two weeks, up to Week 24, wherein after Week 8, dose may be increased or decreased at physician discretion. For first three weeks, previous oral antipsychotic drug (Benzodiazepines or Selective serotonin reuptake inhibitor \[SSRI\]) will be maintained and will cease at Week 3.
DRUGOral atypical anti-psychotic
This is an observational study. Oral atypical anti-psychotic for example, olanzapine, risperidone, quetiapine etc will be administered as per Investigator's discretion.
Sponsors
Xian-Janssen Pharmaceutical Ltd.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, age 18-65 years * Participant must meet the diagnostic criteria for schizophrenia or schizophreniform disorder according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV)-TM * Total course of disease no more than 5 years * According to physician's discretion, participants need to be changed to risperidone long-acting injection and other atypical anti-psychotic drug * 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
Exclusion criteria
* Significant risk of suicidal or violent behavior, as clinically assessed by the Investigator * Have aggressive behavior and excited , restless * History or current symptoms of tardive dyskinesia; neuroleptic malignant syndrome; evidence of dysfunction of liver and kidney and other severe physical diseases; and severe, life-threatening allergic reaction to any drug * Known hypersensitivity to risperidone * Female participant who is pregnant or breastfeeding or planning to become pregnant during the study period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24 | Baseline and Week 24 | The PANSS is a 30-item scale 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 that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Personal and Social Performance (PSP) Score | Baseline and Week 24 | The PSP is a clinician-rated scale that reflects social functioning in 4 domains of behavior (socially useful activities including work and study, personal and social relationships, self care, and disturbing and aggressive behaviors). The total score ranges from 1 to 100 (score of 71 to 100 will have a mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision) divided into 10 equal intervals to rate the degree of difficulty (i=absent to vi=very severe) in each of the 4 domains. |
| Clinical Global Impressions-Severity (CGI-S) Score | Baseline and 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. Higher scores indicate worsening. |
| Percentage of Participants With Relapse at Week 24 | Week 24 | Percentage of participants with relapse was assessed wherein relapse was defined as hospitalization due to the aggravation of psychiatric symptoms of disease condition. |
| Percentage of Participants Attaining Remission Criteria | Month 6 | Remission is defined as a clinical status where for each core symptoms (that are, delusions, conceptual disorganization, hallucinatory behavior, mannerisms and posturing unusual thought content, blunted affect, passive or apathetic social withdrawal and lack of spontaneity and flow of conversation) were assessed at a low-mild symptom intensity level, where such absent, borderline, or mild symptoms do not influence an individual's behavior. |
| Number of Participants With Reasons for Discontinuation From Study Treatment | Month 6 | Number of participants with reasons for discontinuation from study treatment is reported here because participants provided multiple reasons for discontinuation. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Risperidone Risperidone was administered as intramuscular injection at a starting dose of either 25 milligram (mg) or 37.5 mg or 50 mg (starting dose was decided on the basis of the disease severity), every two weeks, up to Week 24, wherein after Week 8, dose may had been increased or decreased at Investigator's discretion. For first three weeks, previous oral antipsychotic drug (benzodiazepines or selective serotonin reuptake inhibitor \[SSRI\]) was maintained and ceased at Week 3. | 396 |
| Oral Atypical Anti-psychotic Oral atypical anti-psychotic for example, olanzapine, risperidone, quetiapine etc was administered as per Investigator's discretion. | 243 |
| Total | 639 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 314 | 175 |
Baseline characteristics
| Characteristic | Risperidone | Oral Atypical Anti-psychotic | Total |
|---|---|---|---|
| Age, Continuous | 27.4 Years STANDARD_DEVIATION 9.44 | 32.2 Years STANDARD_DEVIATION 11.62 | 29.2 Years STANDARD_DEVIATION 10.57 |
| Sex: Female, Male Female | 190 Participants | 136 Participants | 326 Participants |
| Sex: Female, Male Male | 206 Participants | 107 Participants | 313 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 73 / 396 | 48 / 244 |
| serious Total, serious adverse events | 11 / 396 | 0 / 244 |
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 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 that ranges from 1 (absent) to 7 (extreme psychopathology). The PANSS total score consists of the sum of all 30 PANSS items and ranges from 30 to 210. Higher scores indicate worsening.
Time frame: Baseline and Week 24
Population: Intent to treat (ITT) population included all randomized participants who received at least one dose of study drug and had relevant efficacy evaluations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Risperidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24 | Baseline | 74.7 units on a scale | Standard Deviation 22.54 |
| Risperidone | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24 | Change at Week 24 | -36.5 units on a scale | Standard Deviation 25.67 |
| Oral Atypical Anti-psychotic | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24 | Baseline | 72.3 units on a scale | Standard Deviation 20.49 |
| Oral Atypical Anti-psychotic | Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at Week 24 | Change at Week 24 | -38.2 units on a scale | Standard Deviation 24.06 |
Secondary
Clinical Global Impressions-Severity (CGI-S) Score
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. Higher scores indicate worsening.
Time frame: Baseline and Week 24
Population: ITT population included all randomized participants who received at least one dose of study drug and had relevant efficacy evaluations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Risperidone | Clinical Global Impressions-Severity (CGI-S) Score | Baseline | 4.5 units on a scale | Standard Deviation 1.15 |
| Risperidone | Clinical Global Impressions-Severity (CGI-S) Score | Week 24 | 1.5 units on a scale | Standard Deviation 1.02 |
| Oral Atypical Anti-psychotic | Clinical Global Impressions-Severity (CGI-S) Score | Baseline | 4.6 units on a scale | Standard Deviation 1.12 |
| Oral Atypical Anti-psychotic | Clinical Global Impressions-Severity (CGI-S) Score | Week 24 | 2.1 units on a scale | Standard Deviation 1.14 |
Secondary
Number of Participants With Reasons for Discontinuation From Study Treatment
Number of participants with reasons for discontinuation from study treatment is reported here because participants provided multiple reasons for discontinuation.
Time frame: Month 6
Population: Analysis population included all enrolled participants.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Risperidone | Number of Participants With Reasons for Discontinuation From Study Treatment | Discontinuation from Treatment (more than 4 weeks) | 65 Participants | — |
| Risperidone | Number of Participants With Reasons for Discontinuation From Study Treatment | Added other anti-psychotics | 10 Participants | — |
| Risperidone | Number of Participants With Reasons for Discontinuation From Study Treatment | Change to other anti-psychotics | 57 Participants | — |
| Risperidone | Number of Participants With Reasons for Discontinuation From Study Treatment | Lost to follow-up | 67 Participants | — |
| Risperidone | Number of Participants With Reasons for Discontinuation From Study Treatment | Withdrawal by participant | 4 Participants | — |
| Risperidone | Number of Participants With Reasons for Discontinuation From Study Treatment | Other (unspecified) | 128 Participants | — |
| Risperidone | Number of Participants With Reasons for Discontinuation From Study Treatment | Physician Decision | 14 Participants | 22.54 |
| Risperidone | Number of Participants With Reasons for Discontinuation From Study Treatment | Lack of efficacy | 10 Participants | — |
| Risperidone | Number of Participants With Reasons for Discontinuation From Study Treatment | Adverse event | 24 Participants | — |
| Oral Atypical Anti-psychotic | Number of Participants With Reasons for Discontinuation From Study Treatment | Lack of efficacy | 2 Participants | — |
| Oral Atypical Anti-psychotic | Number of Participants With Reasons for Discontinuation From Study Treatment | Adverse event | 3 Participants | — |
| Oral Atypical Anti-psychotic | Number of Participants With Reasons for Discontinuation From Study Treatment | Discontinuation from Treatment (more than 4 weeks) | 7 Participants | — |
| Oral Atypical Anti-psychotic | Number of Participants With Reasons for Discontinuation From Study Treatment | Withdrawal by participant | 0 Participants | — |
| Oral Atypical Anti-psychotic | Number of Participants With Reasons for Discontinuation From Study Treatment | Added other anti-psychotics | 3 Participants | — |
| Oral Atypical Anti-psychotic | Number of Participants With Reasons for Discontinuation From Study Treatment | Physician Decision | 11 Participants | 20.49 |
| Oral Atypical Anti-psychotic | Number of Participants With Reasons for Discontinuation From Study Treatment | Change to other anti-psychotics | 18 Participants | — |
| Oral Atypical Anti-psychotic | Number of Participants With Reasons for Discontinuation From Study Treatment | Other (unspecified) | 106 Participants | — |
| Oral Atypical Anti-psychotic | Number of Participants With Reasons for Discontinuation From Study Treatment | Lost to follow-up | 39 Participants | — |
Secondary
Percentage of Participants Attaining Remission Criteria
Remission is defined as a clinical status where for each core symptoms (that are, delusions, conceptual disorganization, hallucinatory behavior, mannerisms and posturing unusual thought content, blunted affect, passive or apathetic social withdrawal and lack of spontaneity and flow of conversation) were assessed at a low-mild symptom intensity level, where such absent, borderline, or mild symptoms do not influence an individual's behavior.
Time frame: Month 6
Population: ITT population included all randomized participants who received at least one dose of study drug and had relevant efficacy evaluations.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Risperidone | Percentage of Participants Attaining Remission Criteria | 46 Percentage of Participants | 22.54 |
| Oral Atypical Anti-psychotic | Percentage of Participants Attaining Remission Criteria | 68 Percentage of Participants | 20.49 |
Secondary
Percentage of Participants With Relapse at Week 24
Percentage of participants with relapse was assessed wherein relapse was defined as hospitalization due to the aggravation of psychiatric symptoms of disease condition.
Time frame: Week 24
Population: ITT population included all randomized participants who received at least one dose of study drug and had relevant efficacy evaluations.
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Risperidone | Percentage of Participants With Relapse at Week 24 | 0.5 Percentage of Participants | 22.54 |
| Oral Atypical Anti-psychotic | Percentage of Participants With Relapse at Week 24 | 1.6 Percentage of Participants | 20.49 |
Secondary
Total Personal and Social Performance (PSP) Score
The PSP is a clinician-rated scale that reflects social functioning in 4 domains of behavior (socially useful activities including work and study, personal and social relationships, self care, and disturbing and aggressive behaviors). The total score ranges from 1 to 100 (score of 71 to 100 will have a mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision) divided into 10 equal intervals to rate the degree of difficulty (i=absent to vi=very severe) in each of the 4 domains.
Time frame: Baseline and Week 24
Population: ITT population included all randomized participants who received at least one dose of study drug and had relevant efficacy evaluations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Risperidone | Total Personal and Social Performance (PSP) Score | Baseline | 52.1 units on a scale | Standard Deviation 17.15 |
| Risperidone | Total Personal and Social Performance (PSP) Score | Week 24 | 88.0 units on a scale | Standard Deviation 10.25 |
| Oral Atypical Anti-psychotic | Total Personal and Social Performance (PSP) Score | Baseline | 52.9 units on a scale | Standard Deviation 16 |
| Oral Atypical Anti-psychotic | Total Personal and Social Performance (PSP) Score | Week 24 | 82.3 units on a scale | Standard Deviation 10.07 |