Rapidly disintegrating risperidone in subjects with schizophrenia or schizoaffective disorder: a summary of ten phase I clinical trials assessing taste, tablet disintegration time, bioequivalence, and tolerability.
BACKGROUND
Schizophrenia and schizoaffective disorder are severe and chronic psychiatric illnesses for which treatment compliance is important in the prevention of relapse. Atypical antipsychotic drugs, such as risperidone, have been found to be effective in the treatment of a range of psychiatric disorders. Although the oral route of administration is generally preferable to injection, some patients (eg, elderly patients or children) find swallowing physically difficult and thus refuse oral treatments. Rapidly disintegrating (RD) oral formulations of these drugs have been developed to improve their acceptability to patients and thus improve compliance.


OBJECTIVE
The aim of this report was to describe the results from clinical studies that have assessed the taste, time to disintegration, and tolerability of RD risperidone tablets, and bioequivalence of RD risperidone tablets (2 x 0.5 mg, 2 mg, and reduced-size 4 mg) versus conventional (CV) risperidone tablets.


METHODS
This study used data from 10 clinical trials conducted between 1996 and 2003. Eight trials were open-label, crossover trials; 2 were pilot trials, and all of the trials were short-term. The results from 2 trials were published previously; the remainder are unpublished trials. Taste, time to dissolution, and tolerability of RD risperidone tablets were assessed, and bioequivalence (based on the guidelines from the European and US health care evaluation agencies) of RD versus CV risperidone tablets were determined for risperidone, the active metabolite (9-hydroxy-risperidone), and the total antipsychotic fraction (sum of risperidone and the active moiety, 9-hydroxy-risperidone).


RESULTS
In total, these trials included 264 subjects(160 patients with schizophrenia or schizoaffective disorder, 104 healthy volunteers; 173 men, 91 women; age range, 20-61 years). The taste of the RD risperidone tablets was rated as "nice" in 54.2% of subjects compared with 18.3% of subjects who rated CV risperidone as "nice." Totals of 28.8% and 49.2% of subjects described the RD risperidone tablets as "sweet" or "other taste" (commonly mint), respectively. A total of 66.7% of subjects rated the 4-mg RD risperidone tablets as "acceptable, but could be improved," while 85.7% rated the lower-dose RD risperidone tablets as "good." The median time to complete disintegration of the RD risperidone tablet was 38.0 seconds. The mean plasma concentration-time profiles of risperidone and the active moiety of RD or CV risperidone tablets were similar, and these 2 risperidone formulations were found to be bioequivalent. The RD and CV risperidone tablets were well tolerated; there were no serious adverse events reported.


CONCLUSIONS
In the 10 studies analyzed, the taste of RD risperidone tablets was found to be acceptable in the majority of healthy subjects and patients with schizophrenia or schizoaffective disorder. In addition, RD risperidone tablets were found to be bioequivalent to CV risperidone tablets.
Thyssen
An
A
Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium. athyssen@prdbe.jnj.com <athyssen@prdbe.jnj.com>
Remmerie
Bart
B
D'Hoore
Peter
P
Kushner
Stuart
S
Mannaert
Erik
E
D000284:Administration, Oral; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D017321:Clinical Trials, Phase I as Topic; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D010349:Patient Compliance; D017060:Patient Satisfaction; D011618:Psychotic Disorders / Q000188:drug therapy*; D011743:Pyrimidines / Q000493:pharmacokinetics; D018967:Risperidone / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics; D012559:Schizophrenia / Q000188:drug therapy*; D012995:Solubility; D013607:Tablets; D013649:Taste; D013810:Therapeutic Equivalency
D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D013607:Tablets; D018967:Risperidone; D000068882:Paliperidone Palmitate