Laffont C.M. (1), Gomeni R. (2), Zheng B. (3), Heidbreder C. (3), Fudala P.J. (3) and Nasser A.F. (3)
(1) Pharmacometrica, La Fouillade, France; (2) Alleantis, Research Triangle Park, NC 27709, USA; (3) Reckitt Benckiser Pharmaceuticals Inc., Richmond, Virginia, VA 23235, USA
Objectives: RBP-7000 is a sustained-release formulation of risperidone being currently developed for the treatment of schizophrenia. RBP-7000 has been designed for once-monthly subcutaneous injection in order to address compliance issues associated with risperidone oral intake. The objective of the present work was to guide RBP-7000 dose selection for future Phase III trials and to evaluate potential advantages of RBP-7000 over existing long-acting injectable antipsychotics. Our work is based on a modeling and simulation approach integrating competitor data from the literature.
Methods: A population pharmacokinetic (PK) model of RBP-7000 was developed to jointly describe the PK of risperidone and 9‐hydroxyrisperidone after single or multiple doses of RBP-7000 (60, 90, or 120 mg) in 90 clinically stable schizophrenic patients. Active moiety (risperidone + 9‐hydroxyrisperidone) plasma concentration-time profiles were simulated using this model for repeated administrations of RBP-7000 at 60, 90 and 120 mg. The simulated profiles were compared to the published data of Risperda® Consta® (risperidone long-acting injection [RLAI]; 25 and 50 mg), administered every two weeks, or Invega® Sustenna® (paliperidone palmitate [PP], 50 and 100 mg equivalent paliperidone) administered once per month [1].
Results: RBP-7000 data were well described by the population PK model. The simulations indicated that the dose of 90 mg of RBP-7000 provided similar active moiety exposure to 25 mg of RLAI under steady-state conditions, and that 60 and 90 mg of RBP-7000 provided similar active moiety plasma levels at steady-state compared to PP at 50 and 100 mg equivalent paliperidone, respectively. RBP-7000 reached effective concentrations immediately after the first administration. Thus, RBP-7000 did not seem to require any loading dose or supplementation with oral risperidone as required for PP and RLAI, respectively.
Conclusions: The results provide useful information regarding target RBP-7000 dose levels and suggest potential benefits of RBP-7000 compared to other long-acting antipsychotics.
References:
[1] Samtani MN, Gopal S, Gassmann-Mayer C, Alphs L, Palumbo JM (2011) Dosing and switching strategies for paliperidone palmitate. CNS Drugs 25:829-845.
Reference: PAGE 23 (2014) Abstr 3161 [www.page-meeting.org/?abstract=3161]
Poster: Drug/Disease modeling - CNS