Abstract
Background
Risperidone (RIS), an atypical antipsychotic drug, is used for the treatment of psychoses
associated with schizophrenia and other psychiatric disorders in adult and pediatric
populations. An oral dispersible tablet formulation of risperidone has been developed.
This study was conducted to provide support for marketing authorization of this drug
in China.
Objective
This study was designed to compare the pharmacokinetic (PK) properties and bioavailability
of 2 RIS formulations—the dispersible formulation (test) and a branded formulation
(reference) in healthy male Chinese volunteers.
Methods
This single-dose, randomized-sequence, open-label, 2-period crossover study involved
22 healthy male Chinese volunteers. Equal numbers of eligible participants were randomly
assigned to receive either the test drug (2 mg) or the same dose of the reference
formulation, followed by a 2-week washout period and administration of the alternate
formulation. The study drugs were administered after a 10-hour overnight fast. Blood
samples were collected before dosing and at 0.33, 0.67, 1, 1.5, 2, 3, 4, 5, 6, 8,
10, 12, 15, 24, 36, 48, 72, and 96 hours after dosing. Plasma concentrations of RIS
and its active metabolite, 9-hydroxyrisperidone (9-OH-RIS), were measured using LC-MS/MS.
The safety profile was evaluated by recording adverse events (AEs), assessed using
physical examination including vital signs, spontaneous reporting, and clinical laboratory
results. The 2 formulations were considered to have met the requirements for bioequivalence
if the 90% CIs for the log-transformed Cmax and AUC values were within the predetermined ranges of 75% to 133% and 80% to 125%,
respectively, according to the guidelines of the State Food and Drug Administration
(SFDA) of China.
Results
All 22 volunteers (mean [SD] age, 22.2 [1.98] years; weight, 64.07 [5.93] kg; height,
173 [5] cm; and body mass index, 21.2 [1.67] kg/m2) that were enrolled completed the study. For RIS, the 90% CIs for the ratios of Cmax, AUC0–t, and AUC0−∞ were 93.2% to 116.7%, 97.9% to 111.3%, and 98.0% to 111.6%, respectively. For 9-OH-RIS,
the 90% CIs were 95.8% to 113.9%, 100.2% to 109.7%, and 100.5% to 110.3%, respectively.
All values were within the predetermined bioequivalence range. Seven AEs were reported
somnolence (4 subjects [9.1%]) and dizziness (3 subjects [6.8%]). All AEs were transient
and considered mild by physicians.
Conclusions
The test (dispersible) and reference tablets met the regulatory criteria for bioequivalence
as defined by the SFDA. Both formulations were well tolerated. Chinese Clinical Trials
registration number: ChiCTR-TRC-12001996.
Key words
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Article info
Publication history
Published online: May 17, 2012
Accepted:
April 25,
2012
Identification
Copyright
© 2012 Elsevier HS Journals, Inc. Published by Elsevier Inc. All rights reserved.
