Xiao Hu (1), Lahar R. Mehta (1), Pratapa Prasad (1)
(1) Biogen, Cambridge, MA
Objectives: To characterize the pharmacokinetic (PK) profiles of fampridine in Japanese patients with multiple sclerosis in a Phase 3 study using sparse PK data.
Methods: One hundred and one subjects were randomized (Week 1) to receive either prolonged-release fampridine 10 mg tablets (n=51) or placebo (n=50) twice daily for 14 weeks. Two sparse post-dose PK samples per patients were taken during Week 9 visit. PK samples were also taken during unscheduled visit. The current data set was compared to historic data set, which were collected from mostly Caucasian subjects. Population PK was developed using NONMEM [1].
Results: The PK profiles in Japanese subjects were consistent with historic PK data, which were collected mostly from Caucasian subjects [2]. The disposition of fampridine was well described using a one-compartment linear model with a first-order absorption rate, using the same structural base model for historic data. No covariate showed significant effect on PK parameters. Visual predictive checks supported the adequacy of the model. The clearance was 41.3 L/h, the volume of distribution was 91.1 L, the absorption rate was 0.168 h-1.
Conclusions: A population PK model was developed to describe the PK in Japanese patients to support further development of fampridine in this population.
References:
[1] Beal SL, Sheiner LB, Boeckmann AJ & Bauer RJ (Eds.) NONMEM Users Guides. 1989-2011. Icon Development Solutions, Ellicott City, Maryland, USA.
[2] Weir S, Gao Y, Henney HR 3rd. Population pharmacokinetics and pharmacodynamics of dalfampridine-ER in healthy volunteers and in patients with multiple sclerosis, Curr Med Res Opin. 2013 Dec;29(12):1637-45.
Study sponsored by: Biogen
Reference: PAGE 25 (2016) Abstr 6027 [www.page-meeting.org/?abstract=6027]
Poster: Drug/Disease modeling - Absorption & PBPK