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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
| Janssen Korea, Ltd., Korea | INDUSTRY |
| Korea Otsuka Pharmaceutical Co., Ltd. | INDUSTRY |
| Sanofi-Synthelabo |
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The main objective of this study was to assess subjective experiences related to secondary negative symptoms and cognitive performance in healthy volunteers in response to multiple doses of paliperidone ER and risperidone in a double-blind, placebo-controlled trial. Adverse events caused by these drugs were also evaluated.
A new oral antipsychotic drug, paliperidone extended-release (ER), has recently been developed and might represent an innovative approach in the treatment of schizophrenia. Paliperidone is 9-hydroxyrisperidone, the chief active metabolite of risperidone. Although paliperidone possesses a pharmacological profile very similar to that of its parent compound, it has many different pharmacokinetic and pharmacodynamic characteristics compared with risperidone (Pani and Marchese, 2009). First, paliperidone ER utilizes an osmotic controlled-release oral delivery system (OROS), resulting in a more stable serum concentration and reduced likelihood of causing unexpected over- or under-dosages due to CYP2D6 genetic variability. Second, paliperidone does not undergo significant hepatic metabolism, and the drug is predominantly excreted by the kidney as an unchanged drug; whereas risperidone is extensively metabolized by the CYP2D6 hepatic enzyme. Third, the off-rate for dissociation from human cloned D2 receptors in tissue culture cells is faster for paliperidone (60 s) compared with risperidone (27 min) (Seeman, 2005). Due to its looser binding to D2 receptors, paliperidone should be associated with a reduced risk of extrapyramidal side effects compared with its parent drug. Fourth, ex vivo studies have indicated that paliperidone injections induce relatively smaller H1 occupancy levels in the brains of animals when compared with similar dosages of risperidone (Schotte, et al. 1995 and 1996). This may contribute to a reduced sedative effect and less weight gain secondary to paliperidone when compared with risperidone. Finally, paliperidone has no relevant affinity toward muscarinic receptors, resulting in the absence of anticholinergic side effects; this is another important benefit compared with risperidone (Schotte, et al. 1996). Therefore, paliperidone would be the drug of choice in young psychotic patients for whom preservation or improvement of cognitive function is critical. All of these properties might be associated with improved efficacy and better tolerability of paliperidone ER compared with risperidone. In support of this view, recent studies (Canuso, et al. 2008 and 2010) demonstrated that switching from risperidone to paliperidone ER resulted in improvements in medication satisfaction, Positive and Negative Syndrome Scale (PANSS) (Kay, et al. 1987) score, and abbreviated Extrapyramidal Symptoms Rating Scale (Chouinard and Margolese, 2005) score. However, to date, no clinical trials have investigated the relative superiority of paliperidone ER over risperidone in terms of effects on cognitive function. Recently, interest in the negative subjective experiences secondary to antipsychotic medications has been renewed, as these experiences are key factors in adherence and clinical outcomes (Awad, 1993; van Putten and May, 1978). Artaloytia et al. (2006) reported that risperidone induced negative symptoms in healthy volunteers, which might be termed secondary negative symptoms. Therefore, we hypothesized that paliperidone ER has a better safety profile in terms of subjective experiences and cognitive function compared with risperidone. Research on the effects of antipsychotic drugs on subjective experiences and cognitive function in patients with schizophrenia may be hampered by numerous confounding factors, such as pathological features of the illness, patient motivation, or concomitant medications. Investigating the effects of antipsychotic drugs in healthy subjects provides a method for controlling these variables. Therefore, the main objective of this study was to assess subjective experiences related to secondary negative symptoms and cognitive performance in healthy volunteers in response to multiple doses of paliperidone ER and risperidone in a double-blind, placebo-controlled trial. Adverse events caused by these drugs were also evaluated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| risperidone | Experimental | Drug: risperidone 3mg, PO two times Groups: risperidone |
|
| placebo | Placebo Comparator | drug: lactose, PO 3 times group: placebo |
|
| paliperidone ER | Experimental | drug : Paliperidone ER 6mg PO, two times group: paliperidone ER |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| risperidone | Drug | risperidone 3mg, PO, 3 times |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of Negative Symptoms and Neuroleptic Induced Deficit Syndromes by Objective Rating Scales | SANS(Scale for the Assessment of Negative Symptoms), NIDSS(Neuroleptic induced Deficit Syndrome Scale) In NIDSS, the average of number 1 to 5 is blunted affect, the average of number 16 to 20 is avolition, the average of number 6 to 15 is cognition, the average of all score is total. Minimum of NIDSS(avolition, blunted affect, cognition, total) is -3, maximum is +3.(subscale score and total) '+' is better outcome, '-' is worse outcome. Minimum of SANS-Global score for alogia and blunted affect is 0, Maximum of SANS-Global score for alogia and blunted affect is 5 The higher number is worse outcome. The zeros are measured and Calcuated value This outcome measure is reporting a change between baseline and 2hr after third medication. | baseline and 2hr after third medication |
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of Adverse Events by Objective Rating Scales and Self Report Scales | DIEPSS(Drug-Induced Extrapyramidal Symptoms Scale), VAS(Visual analog scale);mental sedation (alert-drowsy, muzzy-clear headed, mentally slow-quick witted, attentive-dreamy), physical sedation (strong-feeble, well coordinated-clumsy, lethargic-energetic, incompetent-proficient), tranquilization (calm-excited, contented-discontented, troubled-tranquil, tense-relaxed), and other types of feelings (happy-sad, antagonistic-amicable, interested-bored, withdrawn-gregarious) Minimum of VAS(Mental sedation score,Physical sedation score,Total score) is 0, Maximum is 10. VAS-total score is average of all subscale scores. Minimum of DIEPSS is 0, Maximum is 4. The higher number is worse outcome. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 2hr after third medication. |
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Inclusion Criteria:
Exclusion Criteria:
Anyone who:
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| Name | Affiliation | Role |
|---|---|---|
| Young-chul Chung, M.D., Ph.D. | Chonbuk National University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Chonbuk national university hospital | Jeonju | South Korea |
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| ID | Title | Description |
|---|---|---|
| FG000 | Risperidone | Drug: risperidone Groups: risperidone |
| FG001 | Placebo | drug: lactose group: placebo |
| FG002 | Paliperidone ER | Drug: Paliperidone ER Groups: Paliperidone ER |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Risperidone | Drug: risperidone Groups: risperidone |
| BG001 | Placebo | drug: lactose group: placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Assessment of Negative Symptoms and Neuroleptic Induced Deficit Syndromes by Objective Rating Scales | SANS(Scale for the Assessment of Negative Symptoms), NIDSS(Neuroleptic induced Deficit Syndrome Scale) In NIDSS, the average of number 1 to 5 is blunted affect, the average of number 16 to 20 is avolition, the average of number 6 to 15 is cognition, the average of all score is total. Minimum of NIDSS(avolition, blunted affect, cognition, total) is -3, maximum is +3.(subscale score and total) '+' is better outcome, '-' is worse outcome. Minimum of SANS-Global score for alogia and blunted affect is 0, Maximum of SANS-Global score for alogia and blunted affect is 5 The higher number is worse outcome. The zeros are measured and Calcuated value This outcome measure is reporting a change between baseline and 2hr after third medication. | Posted | Mean | Standard Deviation | units on a scale | baseline and 2hr after third medication |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Risperidone | Drug: risperidone Groups: risperidone |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort(vomiting) | Gastrointestinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| sedation | Gastrointestinal disorders | Systematic Assessment |
The sample size was small, which presents higher risk of a type II error. The time of assessment after administering placebo or risperidone was noon to 2 PM, which may have contributed to the increased reports of sedation
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Youngchul Chung | Chonbuk National University Hospital | +82-63-250-2185 | chungyc@chonbuk.ac.kr |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D018967 | Risperidone |
| D000068882 | Paliperidone Palmitate |
| ID | Term |
|---|---|
| D011744 | Pyrimidinones |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| INDUSTRY |
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| paliperidone ER | Drug | paliperidone ER 6mg, PO,3 times |
|
|
| placebo | Drug | lactose PO, 3times |
|
| baseline and 2hr after third medication |
| Assessment of Adverse Events by Objective Rating Scales and Self Report Scales | DIEPSS(Drug-Induced Extrapyramidal Symptoms Scale), VAS(Visual analog scale);mental sedation (alert-drowsy, muzzy-clear headed, mentally slow-quick witted, attentive-dreamy), physical sedation (strong-feeble, well coordinated-clumsy, lethargic-energetic, incompetent-proficient), tranquilization (calm-excited, contented-discontented, troubled-tranquil, tense-relaxed), and other types of feelings (happy-sad, antagonistic-amicable, interested-bored, withdrawn-gregarious) Minimum of VAS is 0, Maximum is 10 Minimum of DIEPSS is 0, Maximum is 4 The higher number is worse outcome. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 50hr after third medication. | baseline and 50hr after third medication |
| Assessment of Cognitive Functioning-1 | CNT(Computerized Neuro-Cognitive Function Test System); The tests included a word fluency test. All of the assessments except the CNT were conducted immediately prior to administration of the medication and at 2 (for risperidone and placebo) or 24 h (for paliperidone ER) after the first and third administrations of the study medications. Minimum of Wisconsin card sorting test-Category completed is 0, Maximum is 6, the lower number is worse outcome. Minimum of Wisconsin card sorting test-Perseverative response and Trials to complete is 0, Maximum is 128, the lower number is worse outcome. Minimum of Wisconsin card sorting test-Perseverative error is 0, Maximum is 128, the higher number is worse outcome. Minimum of Word-fluency test is 0 and no maximum value, the higher number is better outcome. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 50hr after third medication. | baseline and 50hr after third medication |
| Symptoms Assessment by Objective Rating Scales | SANS(Scale for the Assessment of Negative Symptoms), NIDSS(Neuroleptic induced Deficit Syndrome Scale) Minimum of NIDSS is -3, maximum of NIDSS is +3. '+' is better outcome, '-' is worse outcome. Minimum of SNAS-Global score is 0, Maximum of SNAS-Global score is 5 The higher number is worse outcome. The zeros are measured and Calcuated value. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 50hr after third medication. | baseline and 50hr after third medication |
| Assessment of Cognitive Functioning-2 | CNT(Computerized Neuro-Cognitive Function Test System); The tests included the Stroop test, Trail-Making Test B (TMT B). All of the assessments except the CNT were conducted immediately prior to administration of the medication and at 2 (for risperidone and placebo) or 24 h (for paliperidone ER) after the first and third administrations of the study medications Minimum of Stroop test is 0, no maximum limit, the higher number is worse outcome. Minimum of Trail making test B is 0 and no maximum limit, the higher number is worse outcome. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 50hr after third medication. | baseline and 50hr after third medication |
| Assessment of Cognitive Functioning-3 | CNT(Computerized Neuro-Cognitive Function Test System); The tests included Wisconsin Card-Sorting Test (WCST). All of the assessments except the CNT were conducted immediately prior to administration of the medication and at 2 (for risperidone and placebo) or 24 h (for paliperidone ER) after the first and third administrations of the study medications. Minimum of Wisconsin card sorting test-Category completed is 0, Maximum is 6, the lower number is worse outcome. Minimum of Wisconsin card sorting test-Perseverative response and Trials to complete is 0, Maximum is 128, the lower number is worse outcome. Minimum of Wisconsin card sorting test-Trials to complete first category trials is 0, Maximum is 128 and minimum of Wisconsin card sorting test-Perseverative error is 0, Maximum is 128, the higher number is worse outcome. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 50hr after th | baseline and 50hr after third medication |
| BG002 |
| Paliperidone ER |
Drug: Paliperidone ER Groups: Paliperidone ER |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Drug: risperidone Groups: risperidone
| OG001 | Placebo | drug: lactose group: placebo |
| OG002 | Paliperidone ER | Drug: Paliperidone ER Groups: Paliperidone ER |
|
|
| Secondary | Assessment of Adverse Events by Objective Rating Scales and Self Report Scales | DIEPSS(Drug-Induced Extrapyramidal Symptoms Scale), VAS(Visual analog scale);mental sedation (alert-drowsy, muzzy-clear headed, mentally slow-quick witted, attentive-dreamy), physical sedation (strong-feeble, well coordinated-clumsy, lethargic-energetic, incompetent-proficient), tranquilization (calm-excited, contented-discontented, troubled-tranquil, tense-relaxed), and other types of feelings (happy-sad, antagonistic-amicable, interested-bored, withdrawn-gregarious) Minimum of VAS(Mental sedation score,Physical sedation score,Total score) is 0, Maximum is 10. VAS-total score is average of all subscale scores. Minimum of DIEPSS is 0, Maximum is 4. The higher number is worse outcome. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 2hr after third medication. | Posted | Mean | Standard Deviation | units on a scale | baseline and 2hr after third medication |
|
|
|
| Secondary | Assessment of Adverse Events by Objective Rating Scales and Self Report Scales | DIEPSS(Drug-Induced Extrapyramidal Symptoms Scale), VAS(Visual analog scale);mental sedation (alert-drowsy, muzzy-clear headed, mentally slow-quick witted, attentive-dreamy), physical sedation (strong-feeble, well coordinated-clumsy, lethargic-energetic, incompetent-proficient), tranquilization (calm-excited, contented-discontented, troubled-tranquil, tense-relaxed), and other types of feelings (happy-sad, antagonistic-amicable, interested-bored, withdrawn-gregarious) Minimum of VAS is 0, Maximum is 10 Minimum of DIEPSS is 0, Maximum is 4 The higher number is worse outcome. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 50hr after third medication. | Posted | Mean | Standard Deviation | units on a scale | baseline and 50hr after third medication |
|
|
|
| Secondary | Assessment of Cognitive Functioning-1 | CNT(Computerized Neuro-Cognitive Function Test System); The tests included a word fluency test. All of the assessments except the CNT were conducted immediately prior to administration of the medication and at 2 (for risperidone and placebo) or 24 h (for paliperidone ER) after the first and third administrations of the study medications. Minimum of Wisconsin card sorting test-Category completed is 0, Maximum is 6, the lower number is worse outcome. Minimum of Wisconsin card sorting test-Perseverative response and Trials to complete is 0, Maximum is 128, the lower number is worse outcome. Minimum of Wisconsin card sorting test-Perseverative error is 0, Maximum is 128, the higher number is worse outcome. Minimum of Word-fluency test is 0 and no maximum value, the higher number is better outcome. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 50hr after third medication. | Posted | Mean | Standard Deviation | scores on a scale | baseline and 50hr after third medication |
|
|
|
| Secondary | Symptoms Assessment by Objective Rating Scales | SANS(Scale for the Assessment of Negative Symptoms), NIDSS(Neuroleptic induced Deficit Syndrome Scale) Minimum of NIDSS is -3, maximum of NIDSS is +3. '+' is better outcome, '-' is worse outcome. Minimum of SNAS-Global score is 0, Maximum of SNAS-Global score is 5 The higher number is worse outcome. The zeros are measured and Calcuated value. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 50hr after third medication. | Posted | Mean | Standard Deviation | units on a scale | baseline and 50hr after third medication |
|
|
|
| Secondary | Assessment of Cognitive Functioning-2 | CNT(Computerized Neuro-Cognitive Function Test System); The tests included the Stroop test, Trail-Making Test B (TMT B). All of the assessments except the CNT were conducted immediately prior to administration of the medication and at 2 (for risperidone and placebo) or 24 h (for paliperidone ER) after the first and third administrations of the study medications Minimum of Stroop test is 0, no maximum limit, the higher number is worse outcome. Minimum of Trail making test B is 0 and no maximum limit, the higher number is worse outcome. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 50hr after third medication. | Posted | Mean | Standard Deviation | milliseconds | baseline and 50hr after third medication |
|
|
|
| Secondary | Assessment of Cognitive Functioning-3 | CNT(Computerized Neuro-Cognitive Function Test System); The tests included Wisconsin Card-Sorting Test (WCST). All of the assessments except the CNT were conducted immediately prior to administration of the medication and at 2 (for risperidone and placebo) or 24 h (for paliperidone ER) after the first and third administrations of the study medications. Minimum of Wisconsin card sorting test-Category completed is 0, Maximum is 6, the lower number is worse outcome. Minimum of Wisconsin card sorting test-Perseverative response and Trials to complete is 0, Maximum is 128, the lower number is worse outcome. Minimum of Wisconsin card sorting test-Trials to complete first category trials is 0, Maximum is 128 and minimum of Wisconsin card sorting test-Perseverative error is 0, Maximum is 128, the higher number is worse outcome. The score ranges are for subscale score. This outcome measure is reporting a change between baseline and 50hr after th | Posted | Mean | Standard Deviation | trials | baseline and 50hr after third medication |
|
|
|
| 2 |
| 11 |
| 5 |
| 11 |
| EG001 | Placebo | drug: lactose group: placebo | 0 | 12 | 2 | 12 |
| EG002 | Paliperidone ER | Drug: Paliperidone ER Groups: Paliperidone ER | 0 | 11 | 0 | 11 |
| sedation | Nervous system disorders | Non-systematic Assessment |
|
| abdominal discomfort | Gastrointestinal disorders | Systematic Assessment |
|
| dizziness | Nervous system disorders | Systematic Assessment |
|
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| D007555 |
| Isoxazoles |
| D001393 | Azoles |
|
| VAS-Physical sedation score |
|
| DIEPSS-Bradykinesia score |
|
|
| VAS-Physical sedation score |
|
| DIEPSS-Bradykinesia score |
|
|
| Word-fluency test-"ㄱ" |
|
| Word-fluency test-"ㅅ" |
|
| Word-fluency test-"ㅇ" |
|
|
| NIDSS-Cognition |
|
| NIDSS-Total |
|
| SANS-Global score for alogia |
|
| SANS-Global score for blunted affect |
|
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| Stroop test-Interference score |
|
| Trail making test B |
|
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| Wisconsin card sorting test-Perseverative error |
|
| WCST-Trials to complete first category trials |
|