T. Funaki(1), Y. Gao(2), R. Wada(2), K. Nakai(1), K. Miura(1), H. Kinoshita(1)
(1)Chugai Pharmaceutical Co. Ltd., 1-9, Kyobashi 2-Chome, Chuo-ku, Tokyo, 104-8301 Japan; (2)Pharsight Corporation, 800 W. El Camino Real, Suite 200, Mountain View, California 94040, U.S.A.
Computer-assisted trial design (CATD) approach in drug development has recently been increasing to assure qualitative and efficient conduct of clinical trails. Pegylated interferon α-2a (PEG-IFN) is interferon α-2a in which one branched polyethylene glycol molecule with an average molecular weight of 40K daltons is conjugated. The half-life of pegylation increases, thereby providing greater exposure and efficacy and allowing to be once a week administration. In this study, CATD model for PEG-IFN was established to investigate the relationship between 2’, 5’-oligoadenylate synthetase (2’,5’-OAS) activity as PD marker and efficacy of PEG-IFN, where once a week administration was assumed to be done for 48 weeks and assumed to be evaluated efficacy (virological and biochemical responses) at weeks 48 and 72.
The population PK/PD model established in a healthy volunteer study was used to establish the CATD model, where an indirect response model (stimulation – kin) was used to describe PD of PEG-IFN. The literature data of virologic responses, biochemical responses and dropout rates were used to predict the possible range of clinical responses. The simulated 2’,5’-OAS activity at week 48 was used to link PK/PD to clinical response since observed 2’,5’-OAS activity at week 48 was not available in healthy subjects.
The current CATD model well describes the virological and biochemical responses at weeks 48 and 72, where a single Emax model was used to describe the relationship between efficacy and PD marker/dose. These results confirm the value of applying the CATD approach to support the clinical development of PEG-IFN as well as other potential products.
Reference: PAGE 12 () Abstr 380 [www.page-meeting.org/?abstract=380]
Poster: poster