Different Safety Profile of Risperidone and Paliperidone Extended-release
Information source: Chonbuk National University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Schizophrenia
Intervention: risperidone (Drug); paliperidone ER (Drug); placebo (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: Chonbuk National University Hospital Official(s) and/or principal investigator(s): Young-chul Chung, M.D., Ph.D., Principal Investigator, Affiliation: Chonbuk National University Hospital
Summary
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.
Clinical Details
Official title: Different Safety Profile of Risperidone and Paliperidone Extended-release: a Double-blind, Placebo-controlled Trial With Healthy Volunteers
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator)
Primary outcome: Assessment of Negative Symptoms and Neuroleptic Induced Deficit Syndromes by Objective Rating Scales
Secondary outcome: Assessment of Adverse Events by Objective Rating Scales and Self Report ScalesAssessment of Adverse Events by Objective Rating Scales and Self Report Scales Assessment of Cognitive Functioning-1 Symptoms Assessment by Objective Rating Scales Assessment of Cognitive Functioning-2 Assessment of Cognitive Functioning-3
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 38 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Aged 18-38 years and meet no DSM-IV diagnostic criteria as assessed by using the
Structured Clinical Interview for DSM-IV, research version
Exclusion Criteria:
Anyone who:
- Participated in other clinical trials within 30 days from the start of this clinical
trial or is currently participating in one
- Has progressive disease or in unstable medical condition unfit for the trial
- Has been diagnosed in psychiatric terms in the past, depends on psychotropic
substance, or has overdosed or depended on the substance or alcohol (except for
coffee or tobacco) within 1 month from the trial start
- Is suicidal or highly probable of suicides; OR
- Has test results considered clinically meaningful
Locations and Contacts
Chonbuk national university hospital, Chonju, Korea, Republic of
Additional Information
Starting date: June 2010
Last updated: September 21, 2012
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